WHAT’S NEW IN OBSTETRIC ANAESTHESIA · 2018. 6. 11. · Oxytocin-Bolus-Injektion in Dosen von mehreren I.E. eine vorübergehende asymptomatische QT-Arzneimittel-Kompendium der Schweiz

WHAT’S NEW IN OBSTETRIC ANAESTHESIA

Thierry GirardBasel

Montag, 28. März 2011


23.03.11 10:34Arzneimittel-Kompendium der Schweiz

Page 1 of 7http://www.kompendium.ch/MonographieTxt.aspx?lang=de&MonType=fi

!

Fachinformation des Arzneimittel-Kompendium der Schweiz®

Syntocinon®/- SprayNOVARTIS PHARMA

AMZV

ZusammensetzungWirkstoff: Oxytocinum.

HilfsstoffeKonz. f. Inf. Lsg./Inj. Lsg.: Natrii acetas, Ethanolum, Conserv.: Chlorobutanolum hemihydricum 5 mg,Aqua q.s. ad solutionem pro 1 ml.Nasalspray: Conserv.: E216, E218, Chlorobutanolum hemihydricum, Excip. ad solutionem pro 1 ml.

Galenische Form und Wirkstoffmenge pro EinheitKonz. f. Inf. Lsg./Inj. Lsg.: 1 ml enthält 5 I.E. Oxytocin.Nasalspray: 1 ml enthält 40 I.E. Oxytocin.

Indikationen/AnwendungsmöglichkeitenKonz. f. Inf. Lsg./Inj. Lsg. zur parenteralen VerabreichungPräpartalGeburtseinleitung aus medizinischen Gründen, z.B. bei Übertragung, vorzeitigem Blasensprung,Schwangerschaftshypertonie (Präeklampsie).Wehenverstärkung in ausgewählten Fällen von Wehenschwäche.Syntocinon kann auch in früheren Schwangerschaftsstadien als Adjuvans zur Behandlung einesnicht vermeidbaren, unvollständigen oder verhaltenen Abortes indiziert sein.

PostpartalWährend eines Kaiserschnittes nach der Entbindung des Kindes.Prophylaxe und Therapie einer postpartalen Uterusatonie/-hämorrhagie.

NasalsprayFörderung der Milchentleerung und Mastitis-Prophylaxe.

Dosierung/AnwendungGeburtseinleitung oder WehenverstärkungSyntocinon wird als intravenöse Tropfinfusion oder, vorzugsweise, mittels einer Infusionspumpe mitvariabler Geschwindigkeit verabreicht. Für die Tropfinfusion werden 5 I.E. Syntocinon in 500 ml einerphysiologischen Elektrolytlösung (wie z.B. NaCl 0,9%) verdünnt. Diese Lösung enthält 10 milli-I.E./ml.Bei Patientinnen, die kein Natriumchlorid erhalten dürfen, kann stattdessen 5%ige Glukoselösungverwendet werden (s.«Warnhinweise und Vorsichtsmassnahmen»). Um eine gleichmässigeDurchmischung der Infusionslösung sicherzustellen, ist die Flasche oder der Beutel vor derAnwendung mehrmals zu kippen.Eine genaue Kontrolle der Infusionsgeschwindigkeit ist unerlässlich. Anfangs soll sie 1–2 milli-I.E./min = 0,1–0,2 ml/min (2–4 Tropfen/min) betragen. Sie kann unter sorgfältiger Überwachung derfötalen Herzfrequenz sowie der Wehenfrequenz und Wehendauer in Intervallen von nicht weniger als20 min und in Schritten von nicht mehr als 1–2 milli-I.E./min gesteigert werden, bis ein mit einerspontanen Wehentätigkeit vergleichbares Kontraktionsmuster vorliegt. Am oder kurz vor demGeburtstermin wird dies häufig mit einer Infusion von weniger als 10 milli-I.E./min = 1 ml/min (20Tropfen/min) erreicht. Die empfohlene maximale Infusionsgeschwindigkeit beträgt 20 milli-I.E./min =2 ml/min (40 Tropfen/min). Sollten ausnahmsweise höhere Infusionsdosen erforderlich sein, wie z.B.bei intra-uterinem Fruchttod oder zur Geburtseinleitung in einem früheren Schwangerschaftsstadium,wenn der Uterus weniger gut auf Oxytocin anspricht, empfiehlt sich die Anwendung einer höherkonzentrierten Syntocinon-Lösung, z.B. 2! 5 I.E. in 500 ml (= 20 milli-I.E./ml).Wird anstelle der Tropfinfusion eine Pumpe mit variablen Infusionsgeschwindigkeiten verwendet,



muss die für den vorgesehenen Dosisbereich geeignete Konzentration der Lösung denSpezifikationen der Pumpe entsprechend berechnet werden.Während der ganzen Infusionsdauer müssen Häufigkeit, Stärke und Dauer der Kontraktionen sowiedie fötale Herzfrequenz sorgfältig überwacht werden. Sobald eine angemessene Wehentätigkeiterreicht ist, kann die Infusionsgeschwindigkeit vermindert werden. Bei übermässiger Wehentätigkeitund/oder Anzeichen für «fetal distress» ist die Infusion sofort abzubrechen.Wenn bei Frauen am oder kurz vor dem Geburtstermin nach einer Infusion von insgesamt 5 I.E.keine regelmässigen Wehen auftreten, ist es ratsam, den Versuch der Geburtseinleitungabzubrechen; er kann am nächsten Tag mit einer anfänglichen Infusionsgeschwindigkeit vonwiederum 1–2 milli-I.E./min wiederholt werden.Hinweis: Eine versehentliche paravenöse Infusion von Oxytocin ist harmlos.

Sectio caesarea5 I.E. unmittelbar nach der Entbindung des Kindes während 5 Minuten langsam intravenösinfundieren.

Prophylaxe postpartaler UterusblutungenDie übliche Dosis beträgt 5 I.E. und wird nach Ausstossung der Plazenta als i.v. Infusion langsamüber 5 min verabreicht. Alternativ können 5–10 I.E. intramuskulär verabreicht werden. Bei Frauen,denen Syntocinon zur Geburtseinleitung oder Wehenstimulation verabreicht worden ist, soll dieInfusion während der Plazentarperiode und für wenige Stunden danach bei erhöhterEinlaufgeschwindigkeit (20–40 milli-I.E./min) fortgesetzt werden.

Therapie postpartaler Uterusblutungen5 I.E. als langsame i.v.-Infusion über 5 min oder 5–10 I.E. i.m., in schweren Fällen gefolgt von eineri.v. Infusion, wobei 5–20 I.E. Oxytocin in 500 ml einer elektrolythaltigen Lösung mit einerGeschwindigkeit infundiert werden, die nötig ist, um die Uterusatonie zu beherrschen.

Nicht-vermeidbarer, unvollständiger oder verhaltener Abort5 I.E. als langsame i.v.-Infusion über 5 min infundieren oder 5–10 I.E. i.m., nötigenfalls gefolgt voneiner i.v. Infusion von 20–40 milli-I.E./min oder mehr.

Nasalspray1 Sprühstoss (0,1 ml Nasalspray Lösung zu 4 I.E. Oxytocin) in eine der beiden Nasenöffnungen 5min vor dem Stillen oder Abpumpen der Milch.Anwendungsweise: s. «Sonstige Hinweise, Hinweise für die Handhabung».

KontraindikationenÜberempfindlichkeit gegenüber dem Wirkstoff oder einem der Hilfsstoffe gemäss Zusammensetzung.Hypertone Wehentätigkeit; «fetal distress» (sofern die Geburt nicht unmittelbar bevorsteht).Schwere Toxämie; Prädisposition für Fruchtwasserembolie (intra-uteriner Fruchttod, Abruptioplacentae).Alle Zustandsbilder, bei welchen aus fötalen oder mütterlichen Gründen auch eine spontaneWehentätigkeit vermieden werden muss und/oder die vaginale Geburt kontraindiziert ist: z.B.erhebliches Kopf/Becken-Missverhältnis, Lageanomalien; Placenta praevia, Vasa praevia, Abruptioplacentae, Nabelschnurumschlingung oder Vorfall; Überdehnung oder verminderte Resistenz desUterus (Ruptur-Risiko) wie bei Mehrlingsschwangerschaft, Hydramnion, Multipara mit mehr als 4Geburten, ältere Multipara, und bei Vorliegen einer Uterusnarbe nach grösseren operativenEingriffen, einschliesslich klassischer Sectio caesarea.Bei Patientinnen mit einer Wehenschwäche, die auf Oxytocin ungenügend anspricht, und beiPatientinnen mit schwerer Präeklampsie oder schweren kardiovaskulären Störungen soll Syntocinonnicht über lange Zeit infundiert werden.Syntocinon Nasalspray ist nicht für die Anwendung während der Schwangerschaft und Geburtbestimmt.

Warnhinweise und VorsichtsmassnahmenDie Anwendung von Oxytocin soll nur in der Klinik und unter qualifizierter ärztlicher Leitung erfolgen.Eine i.v.-Bolusinjektion soll vermieden werden, da dies zu einer akuten kurzandauernden Hypotoniebegleitet von Flushing und Reflextachykardie führen kann.Eine schnelle i.v.-Injektion von Syntocinon in Dosen von mehreren I.E. kann das Risiko fürArrhythmien und Herzstillstand erhöhen. In einer Studie wurde gezeigt, dass eine schnelle i.v.Oxytocin-Bolus-Injektion in Dosen von mehreren I.E. eine vorübergehende asymptomatische QT-



muss die für den vorgesehenen Dosisbereich geeignete Konzentration der Lösung denSpezifikationen der Pumpe entsprechend berechnet werden.Während der ganzen Infusionsdauer müssen Häufigkeit, Stärke und Dauer der Kontraktionen sowiedie fötale Herzfrequenz sorgfältig überwacht werden. Sobald eine angemessene Wehentätigkeiterreicht ist, kann die Infusionsgeschwindigkeit vermindert werden. Bei übermässiger Wehentätigkeitund/oder Anzeichen für «fetal distress» ist die Infusion sofort abzubrechen.Wenn bei Frauen am oder kurz vor dem Geburtstermin nach einer Infusion von insgesamt 5 I.E.keine regelmässigen Wehen auftreten, ist es ratsam, den Versuch der Geburtseinleitungabzubrechen; er kann am nächsten Tag mit einer anfänglichen Infusionsgeschwindigkeit vonwiederum 1–2 milli-I.E./min wiederholt werden.Hinweis: Eine versehentliche paravenöse Infusion von Oxytocin ist harmlos.

Sectio caesarea5 I.E. unmittelbar nach der Entbindung des Kindes während 5 Minuten langsam intravenösinfundieren.

Prophylaxe postpartaler UterusblutungenDie übliche Dosis beträgt 5 I.E. und wird nach Ausstossung der Plazenta als i.v. Infusion langsamüber 5 min verabreicht. Alternativ können 5–10 I.E. intramuskulär verabreicht werden. Bei Frauen,denen Syntocinon zur Geburtseinleitung oder Wehenstimulation verabreicht worden ist, soll dieInfusion während der Plazentarperiode und für wenige Stunden danach bei erhöhterEinlaufgeschwindigkeit (20–40 milli-I.E./min) fortgesetzt werden.

Therapie postpartaler Uterusblutungen5 I.E. als langsame i.v.-Infusion über 5 min oder 5–10 I.E. i.m., in schweren Fällen gefolgt von eineri.v. Infusion, wobei 5–20 I.E. Oxytocin in 500 ml einer elektrolythaltigen Lösung mit einerGeschwindigkeit infundiert werden, die nötig ist, um die Uterusatonie zu beherrschen.

Nicht-vermeidbarer, unvollständiger oder verhaltener Abort5 I.E. als langsame i.v.-Infusion über 5 min infundieren oder 5–10 I.E. i.m., nötigenfalls gefolgt voneiner i.v. Infusion von 20–40 milli-I.E./min oder mehr.

Nasalspray1 Sprühstoss (0,1 ml Nasalspray Lösung zu 4 I.E. Oxytocin) in eine der beiden Nasenöffnungen 5min vor dem Stillen oder Abpumpen der Milch.Anwendungsweise: s. «Sonstige Hinweise, Hinweise für die Handhabung».

KontraindikationenÜberempfindlichkeit gegenüber dem Wirkstoff oder einem der Hilfsstoffe gemäss Zusammensetzung.Hypertone Wehentätigkeit; «fetal distress» (sofern die Geburt nicht unmittelbar bevorsteht).Schwere Toxämie; Prädisposition für Fruchtwasserembolie (intra-uteriner Fruchttod, Abruptioplacentae).Alle Zustandsbilder, bei welchen aus fötalen oder mütterlichen Gründen auch eine spontaneWehentätigkeit vermieden werden muss und/oder die vaginale Geburt kontraindiziert ist: z.B.erhebliches Kopf/Becken-Missverhältnis, Lageanomalien; Placenta praevia, Vasa praevia, Abruptioplacentae, Nabelschnurumschlingung oder Vorfall; Überdehnung oder verminderte Resistenz desUterus (Ruptur-Risiko) wie bei Mehrlingsschwangerschaft, Hydramnion, Multipara mit mehr als 4Geburten, ältere Multipara, und bei Vorliegen einer Uterusnarbe nach grösseren operativenEingriffen, einschliesslich klassischer Sectio caesarea.Bei Patientinnen mit einer Wehenschwäche, die auf Oxytocin ungenügend anspricht, und beiPatientinnen mit schwerer Präeklampsie oder schweren kardiovaskulären Störungen soll Syntocinonnicht über lange Zeit infundiert werden.Syntocinon Nasalspray ist nicht für die Anwendung während der Schwangerschaft und Geburtbestimmt.

Warnhinweise und VorsichtsmassnahmenDie Anwendung von Oxytocin soll nur in der Klinik und unter qualifizierter ärztlicher Leitung erfolgen.Eine i.v.-Bolusinjektion soll vermieden werden, da dies zu einer akuten kurzandauernden Hypotoniebegleitet von Flushing und Reflextachykardie führen kann.Eine schnelle i.v.-Injektion von Syntocinon in Dosen von mehreren I.E. kann das Risiko fürArrhythmien und Herzstillstand erhöhen. In einer Studie wurde gezeigt, dass eine schnelle i.v.Oxytocin-Bolus-Injektion in Dosen von mehreren I.E. eine vorübergehende asymptomatische QT-


! CLINICAL INVESTIGATIONSAnesthesiology 2008; 108:802–11 Copyright © 2008, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc.

Hemodynamic Changes Associated with Spinal Anesthesiafor Cesarean Delivery in Severe PreeclampsiaRobert A. Dyer, F.C.A. (S.A.),* Jenna L. Piercy, F.C.A. (S.A.),† Anthony R. Reed, F.R.C.A.,† Carl J. Lombard, Ph.D.,‡Leann K. Schoeman, F.C.O.G. (S.A.),§ Michael F. James, Ph.D."

Background: Hemodynamic responses to spinal anesthesia(SA) for cesarean delivery in patients with severe preeclampsia arepoorly understood. This study used a beat-by-beat monitor of cardiacoutput (CO) to characterize the response to SA. The hypothesis wasthat CO would decrease from baseline values by less than 20%.

Methods: Fifteen patients with severe preeclampsia con-sented to an observational study. The monitor employed usedpulse wave form analysis to estimate nominal stroke volume.Calibration was by lithium dilution. CO and systemic vascularresistance were derived from the measured stroke volume,heart rate, and mean arterial pressure. In addition, the hemo-dynamic effects of phenylephrine, the response to delivery andoxytocin, and hemodynamics during recovery from SA wererecorded. Hemodynamic values were averaged for defined timeintervals before, during, and after SA.

Results: Cardiac output remained stable from induction of SAuntil the time of request for analgesia. Mean arterial pressureand systemic vascular resistance decreased significantly fromthe time of adoption of the supine position until the end ofsurgery. After oxytocin administration, systemic vascular resis-tance decreased and heart rate and CO increased. Phenyleph-rine, 50 !g, increased mean arterial pressure to above targetvalues and did not significantly change CO. At the time ofrecovery from SA, there were no clinically relevant changesfrom baseline hemodynamic values.

Conclusions: Spinal anesthesia in severe preeclampsia wasassociated with clinically insignificant changes in CO. Phenyl-ephrine restored mean arterial pressure but did not increasematernal CO. Oxytocin caused transient marked hypotension,tachycardia, and increases in CO.

ONLY since 1995, when the first randomized trial on theuse of regional versus general anesthesia for cesarean

delivery in severe preeclampsia was published,1 has spi-nal anesthesia (SA) been considered an option in thishigh-risk group of patients. As recently as 1998, an edi-torial recommended that epidural anesthesia is prefera-ble to SA for cesarean delivery,2 even if the patient hasnot received epidural anesthesia in labor. Many recentstudies suggest that SA is safe in the absence of contra-indications to regional anesthesia.3–6 Some studies haveshown less hypotension and lower vasopressor require-ments than during SA in healthy parturients. One inves-tigation found less hypotension during SA in severe pre-eclamptics than in preterm women in whom fetalweights were similar.4 This eliminated the possibilitythat the more minor degree of hypotension was due to alesser degree of aortocaval compression in preeclampticpatients. Nevertheless, hypotension and placental under-perfusion remain a risk,7 and SA may be associated withmore neonatal acidosis than general anesthesia.8

Most studies have used heart rate (HR) and bloodpressure measurements as surrogate markers of maternalcardiac output (CO). Although pulse and blood pressuremeasurements are of value in assessing the safety of ananesthetic technique, the true goal of SA for cesareandelivery is to maintain maternal CO and uteroplacentalblood flow. In healthy patients, the maximum change inCO has been shown to correlate better with uteropla-cental blood flow than upper arm blood pressure.9 Fur-thermore, in severe preeclampsia, an increased systemicvascular resistance (SVR) could render blood pressure apoor indicator of CO, but the information available onsuch patients during SA is scanty. It was therefore de-cided to investigate CO changes during SA for cesareandelivery in severe preeclampsia. Our hypothesis was thatSA would result in a clinically insignificant change in COin these patients, other than at the time of oxytocinadministration. Also studied were the hemodynamic re-sponses to vasopressors and to delivery and oxytocin. Inaddition, an assessment was made of the hemodynamicsof recovery from SA.

Ultimately, a better understanding of the perioperativehemodynamic changes could contribute to a reductionin perioperative pulmonary edema, renal dysfunction,eclampsia, and neonatal morbidity.

Materials and Methods

Fifteen patients were recruited to this prospective ob-servational study of the hemodynamics of SA for cesar-

This article is accompanied by the following two EditorialViews: Langesæter E: Is it more informative to focus on car-diac output than blood pressure during spinal anesthesia forcesarean delivery in women with severe preeclampsia? ANES-THESIOLOGY 2008; 108:771–2; Pauca AL: Pressure wave analysisis useful to understand the pathophysiology of preeclampsia,but perhaps not the rapid changes during cesarean delivery.ANESTHESIOLOGY 2008; 108:773–4.

!

* Associate Professor, † Senior Specialist Anesthesiologist, " Professor andHead, Department of Anesthesia, § Senior Specialist Obstetrician and Gynecolo-gist, Department of Obstetrics and Gynecology, University of Cape Town.‡ Director, Biostatistics Unit, Medical Research Council, Cape Town, South Africa.

Received from the Department of Anesthesia, University of Cape Town, CapeTown, South Africa. Submitted for publication May 5, 2007. Accepted for pub-lication December 6, 2007. Support was provided solely from institutional and/ordepartmental sources. Presented in part at the Annual Meeting of the ObstetricAnaesthetists’ Association, Sheffield, United Kingdom, June 7–8, 2007.

Address correspondence to Dr. Dyer: D23 Department of Anesthesia, Univer-sity of Cape Town and New Groote Schuur Hospital, Anzio Road, Observatory,Cape Town 7925, South Africa. [email protected]. This article may be ac-cessed for personal use at no charge through the Journal Web site, www.anesthesiology.org.

Anesthesiology, V 108, No 5, May 2008 802

Anesthesiology (2008) vol. 108 (5) pp. 802-11


delivery at a rate that maintains baseline MAP.12 How-ever, this technique was associated with a 47% incidenceof hypertension. In the current study, when target valuesof MAP for vasopressor administration (a 20% decrease

in blood pressure) were reached, CO had not decreasedsignificantly, and in many cases had increased (table 4).This suggests that maintaining blood pressure at thebaseline level in this patient population during SA may

Fig. 3. Ensemble of hemodynamic changes after the administration of oxytocin. (A) Heart rate (HR). At peak effect, HR increasedfrom 84.7 (12.6) to 101.5 (15.9)* beats/min. (B) Mean arterial pressure (MAP). At peak effect, MAP decreased from 114.3 (15.0) to 80.6(15.3)* mmHg. (C) Stroke volume (SV). At peak effect, SV increased from 82.9 (15.9) to 89.1 (17.3) (not significant). (D) Cardiac output(CO). At peak effect, CO increased from 7.0 (1.5) to 9.1 (2.3)* l/min. (E) Systemic vascular resistance (SVR). At peak effect, SVRdecreased from 1,295 (252) to 718 (282)* dyn ! s ! cm!5. * Value significantly different from baseline and postdelivery; P < 0.01.

808 DYER ET AL.

Anesthesiology, V 108, No 5, May 2008

delivery at a rate that maintains baseline MAP.12 How-ever, this technique was associated with a 47% incidenceof hypertension. In the current study, when target valuesof MAP for vasopressor administration (a 20% decrease

in blood pressure) were reached, CO had not decreasedsignificantly, and in many cases had increased (table 4).This suggests that maintaining blood pressure at thebaseline level in this patient population during SA may

Fig. 3. Ensemble of hemodynamic changes after the administration of oxytocin. (A) Heart rate (HR). At peak effect, HR increasedfrom 84.7 (12.6) to 101.5 (15.9)* beats/min. (B) Mean arterial pressure (MAP). At peak effect, MAP decreased from 114.3 (15.0) to 80.6(15.3)* mmHg. (C) Stroke volume (SV). At peak effect, SV increased from 82.9 (15.9) to 89.1 (17.3) (not significant). (D) Cardiac output(CO). At peak effect, CO increased from 7.0 (1.5) to 9.1 (2.3)* l/min. (E) Systemic vascular resistance (SVR). At peak effect, SVRdecreased from 1,295 (252) to 718 (282)* dyn ! s ! cm!5. * Value significantly different from baseline and postdelivery; P < 0.01.

808 DYER ET AL.

Anesthesiology, V 108, No 5, May 2008

2.5 U Oxytocin über 30 Sekunden


J. Phy8iol. (1965), 178, pp. 563-576 563With 5 text-figture.sPrinted in Great Britain

A RELATIONSHIP BETWEEN ADRENALINE AND THE MODEOF ACTION OF OXYTOCIN AND OESTROGEN

ON VASCULAR SMOOTH MUSCLE

BY A. L. HAIGH, SYBIL LLOYD AND MARY PICKFORDFrom the Departments of Veterinary Physiology, and of

Physiology, The University, Edinburgh

(Received 30 October 1964)

Papers already published report that in the normal mammals so farexamined (man, dog and rat, both sexes) oxytocin dilates a number ofvascular beds (Lloyd, 1959a, b; Lloyd & Pickford, 1961; see Haigh,Kitchin & Pickford, 1963). This dilator effect is converted to a constrictorone following chemical blockage of ganglia or peripheral sympatheticnerves, after surgical sympathectomy of the part, and after administra-tion of reserpine. The same change is also induced by subcutaneous orintravenous administration of oestrogens, or when the animal (rat) is innatural oestrus. As a first step towards elucidating the mechanism of theidentical change in the response to oxytocin induced by procedures asdiverse as oestrogen administration and interference with the sympatheticnervous system, it was decided to attempt restoration of the dilator effectof oxytocin after having caused the appearance of the constrictor one.This paper is chiefly concerned with experiments made to this end on anumber of dogs and on two monkeys. Brief reference to some of theseresults has already been made (Haigh, Lloyd & Pickford, 1964; Pickford,1964).

METHODSThe observations were made on a number of dogs of both sexes and on two female

monkeys. All but two of the experiments were acute ones in which the animals wereanaesthetized with pentobarbitone, 26 5 mg/kg body weight, given intravenously; theanimals also received heparin, 5 mg/kg body weight intravenously. Mean blood pressurewas recorded by mercury manometer from the carotid artery. Blood flow through the hindlimb was measured by means of a Pavlov (1887) stromuhr inserted between the cut endsof the femoral vein. When preparations were complete a period of 25-40 min was allowedbefore observations were begun.

Chronic observations were made in one female and one male dog and, in these, leg flowwas measured by means of venous occlusion plethysmography. The diaphragm of theplethysmograph was specially designed with an irregular ovoid opening shaped like thecross-section of a dog's leg. The leg was inserted through this into a thin rubber bag made oftwo breadths of 2 in. diameter colostomy tubing sealed together; in the usual way the rubberbag was attached to the rim of the diaphragm across the opening of the plethysmograph.

36-2


ORIGINAL ARTICLE

Haemodynamic effects of oxytocin in women with severepreeclampsia

E. Langesæter, L.A. Rosseland, A. StubhaugDivision of Anaesthesia and Intensive Care Medicine, Oslo University Hospital – Rikshospitalet, Oslo, Norway

ABSTRACTBackground: Several previous publications demonstrate the significant haemodynamic effects of oxytocin in healthy pregnantwomen, but there is only one publication of the oxytocin effects in women with severe preeclampsia. We investigated the haemo-dynamic effects of oxytocin in women with severe preeclampsia using invasive haemodynamic monitoring.Methods: Eighteen women with severe preeclampsia were included in this observational study. All women had continuous invasivehaemodynamic monitoring during spinal anaesthesia for caesarean section using the LiDCOplus monitor. Preeclamptic patientswere given intravenous boluses of 5 IU oxytocin following delivery.Results: Following an intravenous bolus of 5 IU oxytocin all patients had an increase in heart rate, a decrease in systemic vascularresistance and a decrease in blood pressure. Five patients had a decrease in cardiac output due to an inability to increase strokevolume.Conclusions: The haemodynamic effects of oxytocin in women with severe preeclampsia may be less predictable compared to find-ings in healthy pregnant women, suggesting that oxytocin should be given with caution in women with severe preeclampsia.

!c 2010 Elsevier Ltd. All rights reserved.

Keywords: Severe preeclampsia; Neuraxial anaesthesia; Oxytocin; Cardiac output; Invasive monitoring; LiDCOplus

Introduction

Preeclampsia is a multi-system disease affecting 5–10%of pregnant women.1 The disorder can result in severecomplications including eclampsia, pulmonary oedema,HELLP (haemolysis, elevated liver enzymes, and lowplatelets) syndrome, or renal failure. Preeclampsia is amajor cause of maternal and neonatal morbidity andmortality. Although preeclamptic patients are oftenhypovolaemic with low cardiac output (CO) and in-creased systemic vascular resistance (SVR), this patientgroup is heterogeneous.2 Increased total vascular resis-tance, a high relative wall thickness of the left ventricleand a hypertrophied ventricle are independent predic-tors for developing maternal and fetal complications inpreeclamptic pregnancy.3

Oxytocin is a vasodilator acting on vascular endothe-lial receptors producing a calcium-dependent responsevia stimulation of the nitric oxide pathway.4 There areseveral publications on the haemodynamic effects ofoxytocin in healthy pregnant women,5–7 but only one

previous study showing its effects in severe preeclamp-sia.8 The aim of our observational study was to examinethe haemodynamic response to oxytocin in women withsevere preeclampsia.

Methods

Eighteen women with severe preeclampsia were includedin this study conducted at Oslo University Hospital,Rikshospitalet from August 2005 to August 2008 (regis-tered with clinicaltrials.gov: NCT00403572). The proto-col was approved by The Regional Medical ResearchEthics Committee for Southern Norway and womengave oral and written consent to participate. The onlyexclusion criterion was a contraindication to neuraxialanaesthesia.

Severe preeclampsia was defined as a systolic arterialpressure (SAP) P 160 mmHg with proteinuria, andeither headache, visual disturbance, dyspnoea or epigas-tric pain. Women with a SAP P 160 mmHg and symp-toms were given magnesium sulphate (MgSO4) 4 gintravenously as a loading dose, followed by an infusionof 1 g/h for 24 h.

After monitoring was established with electrocardi-ography and pulse oximetry, a 20-gauge cannula was

Accepted October 2010Correspondence to: Eldrid Langesæter, Division of Anaesthesia andIntensive Care Medicine, Oslo University Hospital – Rikshospitalet,N-0027 Oslo, Norway.E-mail address: [email protected]

International Journal of Obstetric Anesthesia (2011) 20, 26–290959-289X/$ - see front matter !c 2010 Elsevier Ltd. All rights reserved.doi:10.1016/j.ijoa.2010.10.004

www.obstetanesthesia.com

The effects of antihypertensive treatment in pre-eclamptic patients could explain some of the differencesin haemodynamic response to oxytocin in preeclampticas compared to healthy pregnant women, with a muchlesser cardiac compensation to oxytocin in preeclampticpatients. But it is difficult to explain why five patientswith severe preeclampsia were unable to increase SVand had a decrease in CO. Our findings could suggest adiastolic dysfunction in some women with severe pre-eclampsia; they might not be able to increase CO, SV,and HR in the same way as healthy pregnant women inresponse to the vasodilatory effect of oxytocin. Themuch reduced increase in SV in preeclampsia is an inter-esting finding. There are few publications on diastolicdysfunction in preeclamptic patients. Andrietti et al.12

found that women who had previously suffered with pre-eclampsia and had a low plasma volume (present in 30%)had persistent diastolic dysfunction. Aardenburg et al.13

demonstrated that women who had previously sufferedpreeclampsia with subnormal plasma volume were un-able to increase SV with moderate exercise. Further-more, Bamfo et al.14 found that preeclamptic women

had impairment in diastolic function due to both intrin-sic contractility and reduced diastolic filling. Our samplesize was small but our findings suggest that patients withpreeclampsia may have a more unpredictable response tooxytocin. A lower plasma volume could explain whysome women with preeclampsia cannot increase theirSV as a response to the vasodilatory effects of oxytocin.Whatever the cause of the variable haemodynamiceffects of oxytocin in preeclamptic patients, cliniciansshould be aware of the paradoxical effects of oxytocinin a large proportion of these patients.

In our view, patients with severe preeclampsia must betreated on an individual basis. In our department, an arte-rial line is routine during caesarean section in womenwithsevere preeclampsia, and we continue invasive monitor-ing postoperatively. The CO monitor used in this studyhas been validated in other patient groups,15,16 and therehave been recent reports of its use in pregnant wo-men.8,17,18 As we did not use a central venous catheter,CVP was given a value of 5 mmHg. This would not haveany important impact on the calculation of SVR, as CVPis much lower compared to mean arterial pressure.

0 10 20 30 40 50 60 70 80 90 1006

8

10Haemodynamic effects of oxytocin 5 units

CO

(L/m

in)

0 10 20 30 40 50 60 70 80 90 100600800

100012001400

SV

R(d

yns.

s.cm

−5)

0 10 20 30 40 50 60 70 80 90 100

120

140

160SB

P (m

mH

g)

0 10 20 30 40 50 60 70 80 90 10070

80

90

100

SV (m

l)

0 10 20 30 40 50 60 70 80 90 100708090

100110

HR

Time (in seconds)

Fig. 1 The haemodynamic effects of 5 IU oxytocin in 18 patients with severe preeclampsia Oxytocin is given at time 0.

28 Haemodynamics in preeclampsia


OBSTETRICS

Minimum effective bolus dose of oxytocin during electiveCaesarean delivery

A. J. Butwick*, L. Coleman, S. E. Cohen, E. T. Riley and B. Carvalho

Department of Anaesthesia, Stanford University School of Medicine, Stanford, CA, USA

*Corresponding author: Department of Anesthesia (MC:5640), Stanford University School of Medicine,

300 Pasteur Drive, Stanford, CA 94305-5640, USA. E-mail: [email protected]

Background. The aim of this study was to determine the lowest effective bolus dose ofoxytocin to produce adequate uterine tone (UT) during elective Caesarean delivery (CD).

Methods. Seventy-five pregnant patients undergoing elective CD under spinal anaesthesiawere randomized to receive oxytocin (0.5, 1, 3, 5 units) or placebo. UT was assessed by ablinded obstetrician as either adequate or inadequate, and using a verbal numerical scale score(0–10; 0, no UT; 10, optimal UT) at 2, 3, 6, and 9 min after oxytocin administration. Minimumeffective doses of oxytocin were analysed (ED50 and ED95) using logistic regression. Oxytocin-related side-effects (including hypotension) were recorded.

Results. There were no significant differences in the prevalence of adequate UT among thestudy groups at 2 min (73%, 100%, 93%, 100%, and 93% for 0, 0.5, 1, 3, and 5 units oxytocin,respectively). The high prevalence of adequate UT after placebo and low-dose oxytocin pre-cluded determination of the ED50 and ED95. UT scores were significantly lower in patientsreceiving 0 unit oxytocin at 2 and 3 min compared with 3 and 5 units oxytocin (P,0.05,respectively). The prevalence of hypotension was significantly higher after 5 units oxytocin vs 0unit at 1 min (47% vs 7%; P¼0.04).

Conclusions. The routine use of 5 units oxytocin during elective CD can no longer be rec-ommended, as adequate UT can occur with lower doses of oxytocin (0.5–3 units).

Br J Anaesth 2010; 104: 338–43

Keywords: anaesthesia, obstetric; Caesarean section; drug delivery, bolus; uterus, oxytocin

Accepted for publication: December 15, 2009

Oxytocin is routinely administered during elective Caesareandelivery (CD) to initiate and maintain adequate uterine con-tractility after placental delivery. The uterotonic effect ofoxytocin is important in reducing blood loss from the site ofplacental attachment and decreasing the risk of postpartumhaemorrhage. However, adverse haemodynamic effects areknown to occur after i.v. oxytocin, notably tachycardia,hypotension, and ECG changes.1–3 Although many prac-titioners use 5 units oxytocin during elective CD,4 there islimited evidence to substantiate this practice. Smaller bolusdoses of oxytocin are associated with reduced frequency ofadverse effects;2 3 however, few studies have investigated thedose-related effects of an oxytocin bolus for achieving ade-quate uterine tone (UT) during elective CD.2 5 6

The aim of this study was to estimate the minimumeffective dose of oxytocin required to produce adequate

UT at 2 min for 50% (ED50) and 95% (ED95) of patientsundergoing elective CD with spinal anaesthesia.

MethodsAfter obtaining Institutional Review Board approval andwritten informed consent, 75 healthy term patients (!37weeks gestation) undergoing elective CD were enrolled inthis randomized, double-blind, placebo-controlled,dose-ranging study. The study was conducted at LucilePackard Children’s Hospital (Stanford, CA, USA), andpatients were enrolled over a 10-month period (July2008–April 2009).Inclusion criteria were ASA I or II, age between 18 and

40 yr, singleton pregnancies, and elective CD with aPfannensteil incision. All enrolled patients received spinal

# The Author [2010]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.

For Permissions, please email: [email protected]

British Journal of Anaesthesia 104 (3): 338–43 (2010)

doi:10.1093/bja/aeq004


EDITORIAL

Oxytocin protocols during cesarean delivery: time toacknowledge the risk/benefit ratio?

A hormone discovered and synthesized over 50 yearsago, oxytocin is currently used in the majority of birthsin developed countries and a growing number of birthsin the developing world.1 Commonly employed toinduce or augment the process of labor to effect vaginaldelivery, oxytocin is also used as the first line drug torestore uterine tone and minimize postpartum blood lossfollowing cesarean delivery. The purpose of this edito-rial, which is echoed in the review article by Dyer andcolleagues in this issue of IJOA,2 is to illuminate therisks associated with large intravenous (i.v.) bolus dosesof oxytocin administered during cesarean delivery andto advocate an evidenced-based, infusion approach todosing.

The administration of oxytocin is associated with sig-nificant maternal, fetal, and neonatal adverse events.Maternal arrhythmias, hypotension, uterine hyperstimu-lation and hyponatremia,3,4 fetal decreases in oxygen sat-uration (SaO2) related to contraction frequency,5,6 andneonatal seizures, hyperbilirubinemia, or retinal hemor-rhage7,8 have been reported following oxytocin use. Dur-ing cesarean delivery, with oxytocin administeredfollowing delivery, maternal morbidity and mortalityare the most relevant concerns. The 1997–99 triennialaudit of the Confidential Enquiries intoMaternal Deathsin the United Kingdom (UK), reported the deaths of twowomen from cardiovascular instability following an i.v.bolus of oxytocin 10 IU.9 Awareness of these deaths re-sulted in a dose reduction in the UK to an i.v. bolus of5 IU;2 however, even this dose, and the method ofadministration, may cause hypotension, tachycardia, de-creased free water clearance, peripheral flushing, nausea,emesis and signs of myocardial ischemia.10–13

Although practitioners may be aware of these risks,the associated professional liability is the proverbialmountain hidden in plain sight: oxytocin remains thedrug most commonly associated with preventableadverse events during childbirth, and the drug impli-cated in nearly half of all paid obstetric litigationclaims.14 Moreover, the United States Food and DrugAdministration (FDA) has placed a black box warningrestricting oxytocin use (during labor) to medical indi-cations.15 Furthermore, the Institute for Safe Medica-tion Practices (ISMP), an independent, nonprofitorganization whose recommendations are utilized by

groups including the Joint Commission in evaluatingmedication safety, recently added oxytocin to the listof high-alert medications.16 This distinction, whichidentifies drugs ‘‘bearing a heightened risk of harmwhen used in error’’ that may ‘‘require special safe-guards to reduce the risk of error’’, has been appliedto only 11 other specific drugs.16

In an effort to improve patient safety, the cause cele-bre of the contemporary medical community, practitio-ners have questioned the high-dose, non-standardizedoxytocin practices currently in use.17–19 The re-evalua-tion of oxytocin acknowledges the unpredictable thera-peutic index (in which a given dose can result in eitherhypertonic contractions or no discernable effect), useof excessive starting doses, lack of a predetermined,lock-step protocol that predicates increasing doses ondetermination of insufficient lower doses, and practicesthat contribute to normalization of deviance (degrada-tion of professional or technical standards based onindividual experience).17–19 Interestingly, this call toaction stops abruptly at the door of the operating room,despite literature demonstrating that common clinicalpractices result in unnecessary, excessive oxytocin doses.In non-laboring women undergoing cesarean delivery, a‘ceiling effect’ of oxytocin 5 IU is witnessed, beyondwhich no further improvement in uterine tone and bloodloss is observed;20 in laboring women, high doses of oxy-tocin did not obviate the need for additional uterotonicagents.12 Interestingly, a small loading dose of oxytocin(ED 90 = 0.35 IU) has been determined to be sufficientin producing adequate uterine contractions during elec-tive cesarean deliveries in non-laboring women;22 a sim-ilarly low loading dose (ED 90 = 2.99 IU) is required inlaboring women.23 Women who have received oxytocinaugmentation for labor have greater blood loss despitehigher oxytocin doses; this appears to originate fromsignal attenuation and desensitization of the oxytocinreceptors, in a time and concentration dependent man-ner.24–27 Similarly, continued high-dose oxytocin expo-sure in the postpartum period may also lead to acutereceptor desensitization and render the myometrium lessresponsive to additional oxytocin.27

The current guidelines for the administration of oxy-tocin during cesarean delivery are diverse, empiric, andvague. The most recent editions of major obstetric



texts,28–30 either avoid mentioning an oxytocin dose dur-ing cesarean delivery or provide a range of 20-40 IU.The British National Formulary (BNF), the AmericanCollege of Obstetricians and Gynecologists (ACOG),and the Society of Obstetricians and Gynaecologists ofCanada (SOGC) provide guidance for cesarean deliver-ies accompanied with a postpartum hemorrhage (PPH),indicating that a range from 5 IU to 40 IU can be used;further, the SOGC suggests that oxytocin 10 IU can begiven as an i.v. push.

A stepwise, standardized, check-list driven algorithmfor oxytocin use during cesarean delivery is needed toguide practitioners in a clear and concise manner. Thisalgorithm should encompass laboring and non-laboringwomen, as well as prophylactic and therapeutic uses ofoxytocin. More specifically, we believe that the follow-ing points should be incorporated into a protocol: (1)oxytocin should be used in initial doses of less than5 IU; (2) oxytocin should not be administered as a rapidi.v. bolus; (3) an initial rapid infusion of oxytocin shouldbe followed by a maintenance infusion; (4) higher initialand infusion doses of oxytocin offer no clinical benefitand should be avoided; and (5) if it appears that oxyto-cin is not producing effective uterine contractions, otheruterotonic drugs acting via different pathways should beconsidered. We are currently validating a reasonable‘‘Rule of Threes’’ protocol which incorporates these te-nets, is evidence-based, and easy to remember (Table 1).In the application of any protocol, a multidisciplinary,team approach is necessary to assess its impact andmake improvements.

The synthesis and use of oxytocin represents animportant advance to modern obstetric care; however,the significant risk with minimal benefit associated withexcessive doses of oxytocin, particularly when givenas an i.v. bolus, deserves a robust evaluation. Anevidence-based oxytocin protocol that uses low dosesgiven judiciously, incorporates a timed process of uterineassessment, and utilizes alternative uterotonic agents in amore timely manner should improve the quality of care,reduce complications, and enhance the satisfaction andsafety for patients undergoing cesarean delivery. Furtherinvestigation into appropriate oxytocin protocols, cou-pled with the re-evaluation of such protocols for laborinitiation and augmentation, should make the drug’snext golden anniversary a real cause for celebration.

Lawrence C. TsenHarvard Medical School, Department of Anesthesiology,Perioperative and Pain Medicine Brigham and Women’s

Hospital, Boston, MA, USAE-mail: [email protected]

Mrinalini BalkiDepartment of Anesthesia and Pain Management,

University of Toronto, Mount Sinai Hospital,Toronto, ON, Canada

E-mail: [email protected]

References

1. Freeman RK, Nageotte M. A protocol for use of oxytocin. Am JObstet Gynecol 2007;197:445–6.

2. Dyer RA, van Dyk D, Dresner A. The use of uterotonic drugsduring caesarean section. Int J Obstet Anesth 2010;19:313–9.

3. Johnstone M. The cardiovascular effects of oxytocic drugs. Br JAnaesth 1972;44:826–34.

4. D’Souza SW, Lieberman B, Cadman J, Richards B. Oxytocininduction of labour: hyponatraemia and neonatal jaundice. Eur JObstet Gynecol Reprod Biol 1986;22:309–17.

5. Johnson N, van Oudgaarden E, Montague I, McNamara H. Theeffect of oxytocin-induced hyperstimulation on fetal oxygen. BJOG1994;101:805–7.

6. Simpson KR, James DC. Effects of oxytocin-induced uterinehyperstimulation during labor on fetal oxygen status and fetalheart rate patterns. Am J Obstet Gynecol 2008;199:34.e1–5.

7. Beazley JM, Alderman B. Neonatal hyperbilirubinaemia followingthe use of oxytocin in labour. BJOG 1975;82:265–71.

8. Schoenfeld A, Buckman G, Nissenkorn I, Cohen S, Ben-Sira I,Ovadia J. Retinal hemorrhages in the newborn following laborinduced by oxytocin or dinoprostone. Arch Ophthalmol 1985;103:932–4.

9. WhyMothers Die. The Confidential Enquiries intoMaternal Deathsin the United Kingdom 1997–1999. London: RCOG Press; 2001.

10. Thomas JS, Koh SH, Cooper GM. Haemodynamic effects ofoxytocin given as i.v. bolus or infusion on women undergoingCaesarean section. Br J Anaesth 2007;98:116–9.

11. Svanstrom MC, Biber B, Hanes M, Johansson G, Naslund U,Balfors EM. Signs of myocardial ischaemia after injection ofoxytocin: a randomized double-blind comparison of oxytocin andmethylergometrine during Caesarean section. Br J Anaesth2008;100:683–9.

12. Butwick AJ, Coleman L, Cohen SE, Riley ET, Carvalho B.Minimum effective bolus dose of oxytocin during elective Caesar-ean delivery. Br J Anaesth 2010;104:338–43.

13. Pinder AJ, Dresner M, Calow C, Shorten GD, O’Riordan J,Johnson R. Haemodynamic changes caused by oxytocin during

Table 1 Oxytocin protocol for cesarean delivery: ‘‘Rule of threes’’

3 IU oxytocin intravenous loading dose* (administered no faster than 15 seconds12)3 min assessment intervals. If inadequate uterine tone, give 3-IU oxytocin intravenous rescue dose.3 total doses of oxytocin (Initial Load + 2 Rescue Doses)3 IU oxytocin intravenous maintenance dose (3 IU/L at 100 mL/h)3 Pharmacologic options (e.g. ergonovine, carboprost and misoprostol) if inadequate uterine tone persists* An initial dose of 3 IU oxytocin is sufficient for effective uterine contractions for both non-laboring12,21 and laboring23 women. Preferably thisdose should be administered in the form of a rapid infusion, rather than a bolus. Maintenance oxytocin infusion can be administered for up to 8 hfollowing delivery.

244 Editorial

texts,28–30 either avoid mentioning an oxytocin dose dur-ing cesarean delivery or provide a range of 20-40 IU.The British National Formulary (BNF), the AmericanCollege of Obstetricians and Gynecologists (ACOG),and the Society of Obstetricians and Gynaecologists ofCanada (SOGC) provide guidance for cesarean deliver-ies accompanied with a postpartum hemorrhage (PPH),indicating that a range from 5 IU to 40 IU can be used;further, the SOGC suggests that oxytocin 10 IU can begiven as an i.v. push.

A stepwise, standardized, check-list driven algorithmfor oxytocin use during cesarean delivery is needed toguide practitioners in a clear and concise manner. Thisalgorithm should encompass laboring and non-laboringwomen, as well as prophylactic and therapeutic uses ofoxytocin. More specifically, we believe that the follow-ing points should be incorporated into a protocol: (1)oxytocin should be used in initial doses of less than5 IU; (2) oxytocin should not be administered as a rapidi.v. bolus; (3) an initial rapid infusion of oxytocin shouldbe followed by a maintenance infusion; (4) higher initialand infusion doses of oxytocin offer no clinical benefitand should be avoided; and (5) if it appears that oxyto-cin is not producing effective uterine contractions, otheruterotonic drugs acting via different pathways should beconsidered. We are currently validating a reasonable‘‘Rule of Threes’’ protocol which incorporates these te-nets, is evidence-based, and easy to remember (Table 1).In the application of any protocol, a multidisciplinary,team approach is necessary to assess its impact andmake improvements.

The synthesis and use of oxytocin represents animportant advance to modern obstetric care; however,the significant risk with minimal benefit associated withexcessive doses of oxytocin, particularly when givenas an i.v. bolus, deserves a robust evaluation. Anevidence-based oxytocin protocol that uses low dosesgiven judiciously, incorporates a timed process of uterineassessment, and utilizes alternative uterotonic agents in amore timely manner should improve the quality of care,reduce complications, and enhance the satisfaction andsafety for patients undergoing cesarean delivery. Furtherinvestigation into appropriate oxytocin protocols, cou-pled with the re-evaluation of such protocols for laborinitiation and augmentation, should make the drug’snext golden anniversary a real cause for celebration.

Lawrence C. TsenHarvard Medical School, Department of Anesthesiology,Perioperative and Pain Medicine Brigham and Women’s

Hospital, Boston, MA, USAE-mail: [email protected]

Mrinalini BalkiDepartment of Anesthesia and Pain Management,

University of Toronto, Mount Sinai Hospital,Toronto, ON, Canada

E-mail: [email protected]

References

1. Freeman RK, Nageotte M. A protocol for use of oxytocin. Am JObstet Gynecol 2007;197:445–6.

2. Dyer RA, van Dyk D, Dresner A. The use of uterotonic drugsduring caesarean section. Int J Obstet Anesth 2010;19:313–9.

3. Johnstone M. The cardiovascular effects of oxytocic drugs. Br JAnaesth 1972;44:826–34.

4. D’Souza SW, Lieberman B, Cadman J, Richards B. Oxytocininduction of labour: hyponatraemia and neonatal jaundice. Eur JObstet Gynecol Reprod Biol 1986;22:309–17.

5. Johnson N, van Oudgaarden E, Montague I, McNamara H. Theeffect of oxytocin-induced hyperstimulation on fetal oxygen. BJOG1994;101:805–7.

6. Simpson KR, James DC. Effects of oxytocin-induced uterinehyperstimulation during labor on fetal oxygen status and fetalheart rate patterns. Am J Obstet Gynecol 2008;199:34.e1–5.

7. Beazley JM, Alderman B. Neonatal hyperbilirubinaemia followingthe use of oxytocin in labour. BJOG 1975;82:265–71.

8. Schoenfeld A, Buckman G, Nissenkorn I, Cohen S, Ben-Sira I,Ovadia J. Retinal hemorrhages in the newborn following laborinduced by oxytocin or dinoprostone. Arch Ophthalmol 1985;103:932–4.

9. WhyMothers Die. The Confidential Enquiries intoMaternal Deathsin the United Kingdom 1997–1999. London: RCOG Press; 2001.

10. Thomas JS, Koh SH, Cooper GM. Haemodynamic effects ofoxytocin given as i.v. bolus or infusion on women undergoingCaesarean section. Br J Anaesth 2007;98:116–9.

11. Svanstrom MC, Biber B, Hanes M, Johansson G, Naslund U,Balfors EM. Signs of myocardial ischaemia after injection ofoxytocin: a randomized double-blind comparison of oxytocin andmethylergometrine during Caesarean section. Br J Anaesth2008;100:683–9.

12. Butwick AJ, Coleman L, Cohen SE, Riley ET, Carvalho B.Minimum effective bolus dose of oxytocin during elective Caesar-ean delivery. Br J Anaesth 2010;104:338–43.

13. Pinder AJ, Dresner M, Calow C, Shorten GD, O’Riordan J,Johnson R. Haemodynamic changes caused by oxytocin during

Table 1 Oxytocin protocol for cesarean delivery: ‘‘Rule of threes’’

3 IU oxytocin intravenous loading dose* (administered no faster than 15 seconds12)3 min assessment intervals. If inadequate uterine tone, give 3-IU oxytocin intravenous rescue dose.3 total doses of oxytocin (Initial Load + 2 Rescue Doses)3 IU oxytocin intravenous maintenance dose (3 IU/L at 100 mL/h)3 Pharmacologic options (e.g. ergonovine, carboprost and misoprostol) if inadequate uterine tone persists* An initial dose of 3 IU oxytocin is sufficient for effective uterine contractions for both non-laboring12,21 and laboring23 women. Preferably thisdose should be administered in the form of a rapid infusion, rather than a bolus. Maintenance oxytocin infusion can be administered for up to 8 hfollowing delivery.

244 Editorial

EDITORIAL

Oxytocin protocols during cesarean delivery: time toacknowledge the risk/benefit ratio?

A hormone discovered and synthesized over 50 yearsago, oxytocin is currently used in the majority of birthsin developed countries and a growing number of birthsin the developing world.1 Commonly employed toinduce or augment the process of labor to effect vaginaldelivery, oxytocin is also used as the first line drug torestore uterine tone and minimize postpartum blood lossfollowing cesarean delivery. The purpose of this edito-rial, which is echoed in the review article by Dyer andcolleagues in this issue of IJOA,2 is to illuminate therisks associated with large intravenous (i.v.) bolus dosesof oxytocin administered during cesarean delivery andto advocate an evidenced-based, infusion approach todosing.

The administration of oxytocin is associated with sig-nificant maternal, fetal, and neonatal adverse events.Maternal arrhythmias, hypotension, uterine hyperstimu-lation and hyponatremia,3,4 fetal decreases in oxygen sat-uration (SaO2) related to contraction frequency,5,6 andneonatal seizures, hyperbilirubinemia, or retinal hemor-rhage7,8 have been reported following oxytocin use. Dur-ing cesarean delivery, with oxytocin administeredfollowing delivery, maternal morbidity and mortalityare the most relevant concerns. The 1997–99 triennialaudit of the Confidential Enquiries intoMaternal Deathsin the United Kingdom (UK), reported the deaths of twowomen from cardiovascular instability following an i.v.bolus of oxytocin 10 IU.9 Awareness of these deaths re-sulted in a dose reduction in the UK to an i.v. bolus of5 IU;2 however, even this dose, and the method ofadministration, may cause hypotension, tachycardia, de-creased free water clearance, peripheral flushing, nausea,emesis and signs of myocardial ischemia.10–13

Although practitioners may be aware of these risks,the associated professional liability is the proverbialmountain hidden in plain sight: oxytocin remains thedrug most commonly associated with preventableadverse events during childbirth, and the drug impli-cated in nearly half of all paid obstetric litigationclaims.14 Moreover, the United States Food and DrugAdministration (FDA) has placed a black box warningrestricting oxytocin use (during labor) to medical indi-cations.15 Furthermore, the Institute for Safe Medica-tion Practices (ISMP), an independent, nonprofitorganization whose recommendations are utilized by

groups including the Joint Commission in evaluatingmedication safety, recently added oxytocin to the listof high-alert medications.16 This distinction, whichidentifies drugs ‘‘bearing a heightened risk of harmwhen used in error’’ that may ‘‘require special safe-guards to reduce the risk of error’’, has been appliedto only 11 other specific drugs.16

In an effort to improve patient safety, the cause cele-bre of the contemporary medical community, practitio-ners have questioned the high-dose, non-standardizedoxytocin practices currently in use.17–19 The re-evalua-tion of oxytocin acknowledges the unpredictable thera-peutic index (in which a given dose can result in eitherhypertonic contractions or no discernable effect), useof excessive starting doses, lack of a predetermined,lock-step protocol that predicates increasing doses ondetermination of insufficient lower doses, and practicesthat contribute to normalization of deviance (degrada-tion of professional or technical standards based onindividual experience).17–19 Interestingly, this call toaction stops abruptly at the door of the operating room,despite literature demonstrating that common clinicalpractices result in unnecessary, excessive oxytocin doses.In non-laboring women undergoing cesarean delivery, a‘ceiling effect’ of oxytocin 5 IU is witnessed, beyondwhich no further improvement in uterine tone and bloodloss is observed;20 in laboring women, high doses of oxy-tocin did not obviate the need for additional uterotonicagents.12 Interestingly, a small loading dose of oxytocin(ED 90 = 0.35 IU) has been determined to be sufficientin producing adequate uterine contractions during elec-tive cesarean deliveries in non-laboring women;22 a sim-ilarly low loading dose (ED 90 = 2.99 IU) is required inlaboring women.23 Women who have received oxytocinaugmentation for labor have greater blood loss despitehigher oxytocin doses; this appears to originate fromsignal attenuation and desensitization of the oxytocinreceptors, in a time and concentration dependent man-ner.24–27 Similarly, continued high-dose oxytocin expo-sure in the postpartum period may also lead to acutereceptor desensitization and render the myometrium lessresponsive to additional oxytocin.27

The current guidelines for the administration of oxy-tocin during cesarean delivery are diverse, empiric, andvague. The most recent editions of major obstetric




ORIGINAL ARTICLE

General anesthesia for cesarean delivery at a tertiary carehospital from 2000 to 2005: a retrospective analysis and10-year update

A. Palanisamy, A.A. Mitani, L.C. TsenDepartment of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital,Harvard Medical School, Boston, MA, USA

ABSTRACTBackground: Complications from general anesthesia for cesarean delivery are a leading cause of anesthesia-related mortality. As aconsequence, the overall use of general anesthesia in this setting is becoming less common. The impact and implications of thistrend are considered in relation to a similar study performed at our institution 10 years ago.Methods: The hospital database for all cesarean deliveries performed during six calendar years (January 1, 2000 through Decem-ber 31, 2005) was reviewed. The medical records of all parturients who received general anesthesia were examined to collect per-sonal details and data pertinent to the indications for cesarean delivery and general anesthesia, mode of airway management andassociated anesthetic complications.Results: Cesarean deliveries accounted for 23.65% to 31.51% of an annual total ranging from 8543 to 10091 deliveries. The per-centage of cases performed under general anesthesia ranged from 0.5% to 1%. A perceived lack of time for neuraxial anesthesiaaccounted for more than half of the general anesthesia cases each year, with maternal factors accounting for 11.1% to 42.9%. Fail-ures of neuraxial techniques accounted for less than 4% of the general anesthesia cases. There was only one case of difficult intu-bation and no anesthesia-related mortality was recorded.Conclusion: The use of general anesthesia for cesarean delivery is low and declining. These trends may reflect the early and increas-ing use of neuraxial techniques, particularly in parturients with co-existing morbidities. A significant reduction in exposure oftrainees to obstetric general anesthesia has been observed.

!c 2010 Elsevier Ltd. All rights reserved.

Keywords: General anesthesia; Cesarean delivery; Cesarean section; Neuraxial techniques; Regional techniques; Difficult airway;Airway management; Obstetrics

Introduction

The widespread adoption of neuraxial techniques for la-bor analgesia and cesarean delivery anesthesia has beenprompted by a number of benefits and concerns, includ-ing a desire to avoid the potentially difficult maternalairway and the risk of pulmonary aspiration.1–3 In addi-tion, recent population-based evidence indicates thatneuraxial anesthesia might be associated with a lowerincidence of adverse neonatal outcomes and learningdisabilities in children.4,5 It has also been associated withshorter hospital stays following cesarean delivery.6

Despite these findings, a recent meta-analysis failedto confirm an advantage with the use of neuraxial tech-niques versus general anesthesia (GA) in major maternalor neonatal outcomes.7 Moreover, GA remains a neces-sary choice, particularly when there is a perceived lackof time, a contraindication or refusal of neuraxial tech-niques. With fewer cesarean deliveries being performedunder GA, there is a growing concern that anesthesiaproviders, particularly those in training, will have littleor no opportunities to learn and maintain critical skillsfor maternal airway management.8–10 Although ad-vances in anesthetic pharmacology and airway equip-ment have made such airway manipulations safer, theoverall impact on clinical obstetric anesthetic practicehas yet to be determined.

In an effort to assess the indications and implicationsof GA use for cesarean delivery, we evaluated andreported data from our large volume, tertiary care insti-tution during the period of 1990 to 1995.10 The purpose

Accepted July 2010Correspondence to: Lawrence C. Tsen, MD, Department of Anesthe-siology, Perioperative and Pain Medicine, Brigham and Women’sHospital, Harvard Medical School, 75 Francis Street, CWN-L1,Boston, MA 02115, USA.E-mail address: [email protected]




ORIGINAL INVESTIGATIONS IN ANESTHESIOLOGY Anesthesiology 2010; 112:985–92

Copyright © 2010, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins

Simulation-based Training Improves Physicians’Performance in Patient Care in High-stakes ClinicalSetting of Cardiac SurgeryHeinz R. Bruppacher, M.D.,* Syed K. Alam, M.D.,* Vicki R. LeBlanc, Ph.D.,† David Latter, M.D.,‡Viren N. Naik, M.D., M.Ed.,§ Georges L. Savoldelli, M.D., M.Ed.,! C. David Mazer, M.D.,#Matt M. Kurrek, M.D.,** Hwan S. Joo, M.D.††

ABSTRACTBackground: Simulation-based training is useful in improving phy-sicians’ skills. However, no randomized controlled trials have beenable to demonstrate the effects of simulation teaching in real-lifepatient care. This study aimed to determine whether simulation-based training or an interactive seminar resulted in better patientcare during weaning from cardiopulmonary bypass (CPB)—a highstakes clinical setting.Methods: This study was conducted as a prospective, single-blinded,randomized controlled trial. After institutional research board approval,20 anesthesiology trainees, postgraduate year 4 or higher, inexperi-enced inCPBweaning, and 60 patients scheduled for elective coronaryartery bypass grafting were recruited. Each trainee received a teachingsyllabus for CPB weaning 1 week before attempting to wean a patientfromCPB (pretest). One week later, each trainee received a 2-h trainingsession with either high-fidelity simulation-based training or a 2-h inter-active seminar. Each trainee then weaned patients from CPB within 2weeks (posttest) and 5 weeks (retention test) from the intervention.Clinical performance was measured using the validated Anesthesiolo-gists’ Nontechnical Skills Global Rating Scale and a checklist of ex-pected clinical actions.Results: Pretest Global Rating Scale and checklist performanceswere similar. The simulation group scored significantly higher thanthe seminar group at both posttest (Global Rating Scale [mean standard error]: 14.3 0.41 vs. 11.8 0.41, P 0.001; checklist:

89.9 3.0% vs. 75.4 3.0%, P 0.003) and retention test (GlobalRating Scale: 14.1 0.41 vs. 11.7 0.41, P 0.001; checklist:93.2 2.4% vs. 77.0 2.4%, P 0.001).Conclusion: Skills required to wean a patient from CPB can be ac-quired through simulation-based training. Compared with traditionalinteractive seminars, simulation-based training leads to improved per-formance in patient care by senior trainees in anesthesiology.

A T some stage in their educational process, trainees applytheir knowledge to treat patients in real-life clinical set-

tings, before achieving full clinical competency. Patientsafety may be compromised during this period.1 Simulationtechnology has been advocated as a safer method for studentsto learn and practice skills in high-acuity scenarios withoutexposing real patients to the possibility of adverse events.2,3

H owever, investigations into the effectiveness of simulation-based training for dynamic domains involving high stakesand invasive interventions such as in the fields of anesthesi-ology, surgery, critical care, and emergency medicine are lim-ited. T he unpredictable occurrence of medical crises in realpatients makes many outcome studies unfeasible. To providestronger evidence of support, a randomized controlled trialwith assessment in the clinical setting is required to supportsimulation-based training for dynamic domains.

* Clinical Fellow, # Professor and Vice Chair of Research, ††Assistant Professor, Department of Anesthesia, ‡ Associate Profes-sor, Department of Surgery, St. Michael’s Hospital, University ofToronto, Toronto, Ontario, Canada. † Associate Director and Scien-tist II, Wilson Centre, University Health Network & Assistant Profes-sor, Department of Medicine, University of Toronto. § AssociateProfessor, Department of Anesthesia, The Ottawa Hospital, Univer-sity of Ottawa, Ottawa, Ontario, Canada. ! Assistant Professor, Di-vision of Anesthesiology, Faculty of Medicine, University Hospitalsof Geneva, University of Geneva, Geneva, Switzerland. ** AssistantProfessor, Department of Anesthesia, University of Toronto.

Received from Department of Anesthesia, St. Michael’s Hospital,University of Toronto, Toronto, Ontario, Canada. Submitted forpublication August 19, 2009. Accepted for publication December 29,2009. Supported by Physicians’ Services Incorporated Foundation,Toronto, Ontario, Canada.

Address correspondence to Dr. Joo: Department of Anesthesia, St.Michael’s Hospital, University of Toronto, 30 Bond Street, 1-026 Shuter,Toronto, Ontario, Canada M5B 1W8. [email protected]. Infor-mation on purchasing reprints may be found at www.anesthesiology-.org or on the masthead page at the beginning of this issue. ANESTHE-SIOLOGY’s articles are made freely accessible to all readers, for personaluse only, 6 months from the cover date of the issue.

! This article is accompanied by an Editorial View. Please see:Steadman RH: Improving on reality: Can simulation facilitatepractice change? ANESTHESIOLOGY 2010; 112:775–6.

What We Already Know about This Topic

! Simulation training improves skills and management whencrises are subsequently presented in a simulation environ-ment, but whether this translates to real life situations is notknown

What This Article Tells Us That Is New

! Senior anesthesia trainees who received simulation trainingfor weaning from cardiopulmonary bypass performed better inthis situation in real life than those who received traditionalinteractive seminars

Anesthesiology, V 112 • N o 4 985 April 2010

Anesthesiology. 2010 Apr;112(4):985-92


EDITORIAL

Antibiotic prophylaxis for cesarean delivery: always before skinincision!

On the morning of January 23, in the year 1883, the sun,shining through a thin veil of haze, tinted with a pale,orange light the snowbanks at the upper end of McLeanStreet. The long, grey faint shadow of the corner lamp-post, stretching unevenly across the rutted roadway,slowly shortened with the advancing day and swung imper-ceptibly toward the hospital like a monitory finger. A wetsalt chill was in the air, borne in from the sea upon a slug-gish southeast wind. Men passing in the street felt its colddampness through their greatcoats, and women wrappedthemselves more tightly in their shawls as they hurriedback to their firesides. Creeping through the cracks abovethe windows it stole into the wards, a harbinger of evil tothe parents who shivered beneath their blankets.That afternoon, at forty minutes after three, BridgetLogan died of childbed fever.

Frederick Irving, Safe Deliverance, 19421

Such was obstetrics in the days before antiseptics, anti-biotics, and effective pathogen control, when the bestthat could be wished for a woman was that she wouldhave her baby so quickly that the doctor could not ar-rive in time to infect her. In the early 19th century, 1in every 2 women in labor became infected, and 1 in20 died of so-called puerperal fever. Fortunately, suchan era is today largely of historical interest only. How-ever, morbidity due to infection is still a common prob-lem encountered during pregnancy, labor, and thepostpartum period.

Antibiotic prophylaxis to prevent postoperativeinfection is standard for most general surgical proce-dures, and the standard practice is to administer anti-biotics prior to skin incision. This is not controversial,it is evidence-based, and the timing of administrationthat is widely utilized for the majority of surgical proce-dures.2 The obvious rationale for this practice is to havetissue levels of antibiotics present at the time of surgicalincision, a theoretical rationale first shown to be impor-tant for efficacy through elegant animal model experi-ments by Burke.3 However, timing of antibioticprophylaxis has historically been different with regardto cesarean delivery. The clinical trials that demon-strated the efficacy of antibiotic prophylaxis in prevent-ing infection after cesarean delivery all studied theadministration of antibiotics after clamping of the

umbilical cord.4–6 The rationale for this was to avoidany exposure of the neonate to the antibiotics and toprevent any masking of newborn culture results in casesthat carried a risk for newborn infection. In addition,animal experiments suggested only a small decrease inefficacy with administration of antibiotics soon afterskin incision. Antibiotic prophylaxis given at cordclamping was shown to significantly decrease postoper-ative infection in multiple clinical trials, and for manyyears, the standard practice has been to administer theantibiotic prophylaxis for cesarean delivery only afterclamping of the umbilical cord.

Cesarean delivery is one of the most common majoroperations performed today, and rates of complicationsof infection, including resultant increased cost andlength of stay, are higher than for any other comparablesurgery. Despite the long-standing practice of adminis-tering antibiotics prior to skin incision in general surgi-cal procedures, only recently has preoperative timing forcesarean delivery been investigated. In 2007 Sullivanet al. reported results from a randomized, prospective,double-blind trial comparing the administration ofcefazolin 15–60 min prior to skin incision to administra-tion after cord clamping.7 The group receiving the ear-lier antibiotics had less overall infectious morbidityand specifically less endometritis, with no concomitantincrease in any adverse neonatal effects. Other similarstudies have found comparable results.8–11

While many institutions, including our own, adoptedthe practice of administering prophylactic antibiotics forcesarean delivery pre-incision several years ago, societalguidelines often run behind clinical practice, and someclinicians still wait until after infant delivery to adminis-ter the antibiotics. Case in point – in a recent (2009)case-discussion in the New England Journal of Medi-cine, a case of severe streptococcal post-cesarean necro-tizing fasciitis was presented.12 In the published casedescription, the patient, who had a relatively uncompli-cated and elective cesarean, had her antibiotics adminis-tered after umbilical cord clamping. The case discussionincluded the statement that this was ‘‘appropriate pro-phylactic antibiotic coverage.’’ A follow-up letter-to-the-editor challenged this alleged appropriateness, andin reply, even the original authors of the case agreed thatpre-incision antibiotic administration should now be




www.cemach.org.uk


in the Introduction, mean that any maternal deaths thatoccur after 42 completed days following the end of preg-nancy are not included in the overall maternal mortalityrate calculations. However, in this Report, nine womendied of Late Direct causes later than this, and, althoughthese cases are not included in the overall UK maternalmortality rate, the lessons drawn from them are discussedin the relevant Chapters of this Report.

Indirect deathsFor this triennium, the maternal mortality rate from Indi-rect causes, that is from pre-existing or new medical ormental health conditions aggravated by pregnancy such asheart disease or suicide, is 6.72 (95% CI 5.74–7.87) per100 000 maternities. The rate has not significantly changedfrom the 7.71 (95% CI 6.61–8.99) per 100 000 maternities

in the last Report (P = 0.22). The numbers of maternaldeaths from Indirect causes continue to outnumber Directdeaths, as has been seen in the past four Reports (Fig-ures 1.2 and 1.3). Although there has been a significantincrease (P < 0.001) in mortality rates from Indirect causessince 1985, this can probably be explained by far better caseascertainment and inclusion of cases that might have beenconsidered as Coincidental in the past, such as suicides andhormone-dependent malignancies.

Rolling 3-year average mortality ratesTo provide more timely updates on general trends and anyemerging issues that require urgent attention, in futureCMACE will, in the 2 years between the 3-yearly publica-tion of these comprehensive Saving Mothers’ Lives Reports,publish a short annual summary on the rolling 3-year aver-

0

2

4

6

8

10

12

14

16

1985–1987 1988–1990 1991–1993 1994–1996 1997–1999 2000–2002 2003–2005 2006–2008

Rat

e pe

r 100

000

mat

erni

ties

Figure 1.1. Direct and Indirect maternal mortality rates per 100 000 maternities; UK: 1985–2008.

0

1

2

3

4

5

6

7

8

9

10

1985–1987 1988–1990 1991–1993 1994–1996 1997–1999 2000–2002 2003–2005 2006–2008

Rat

e pe

r 100

000

mat

erni

ties

Test for trend over period 1985–2008: P = 0.07

Figure 1.2. Direct maternal mortality rates per 100 000 maternities; UK: 1985–2008.

Chapter 1: The women who died 2006–2008

ª 2011 Centre for Maternal and Child Enquiries (CMACE), BJOG 118 (Suppl. 1), 1–203 33

261 deaths from 2005 to 2008

70% substandard care!


0.00

0.50

1.00

1.50

2.00

2.50

Cardiac disease

Other indirectcauses

Indirectneurological

conditions

Sepsis

Pre-eclampsia andeclampsia

Thrombosis andthromboembolism

Amniotic fluidembolism

Psychiatric causes

Early pregnancydeaths

Haemorrhage

Anaesthesia

Other direct

Indirectmalignancies

Rate per 100 000 maternities

Figure

1.4.Lead

ing

causes

ofmatern

aldeath

per

100000matern

ities;UK:2006–0

8.Other

Indirect

causes

ofdeath

aresep

aratedinto

neu

rological

andothers,

andOther

Direct

inclu

des

fattyliver

andadirect

cancer.

Table

1.6.Matern

aldeath

sbytyp

eofan

tenatal

care;UK:2006–0

8

Dire

ctIndire

ctDire

ctand

Indire

ct

Coincid

ental

Late

Dire

ctAlldeaths

nn

n%

nn

n%

Typeofantenatalcare

Team-based

or‘sh

ared’care

42

68

110

42

16

1127

40

Midwife

only

27

25

52

20

12

266

21

Consultan

t-ledcare

11

32

43

17

73

53

17

Midwife

andGP

64

10

42

113

4

Other

21

31

10

41

Private0

11

00

01

0

Noan

tenatal

care18

23

41

16

12

255

17

Notkn

own

10

10

01

Total

107

154

261

100

50

9320

100

Reaso

nfornoantenatalcare

Death

befo

rebookin

gorafter

miscarriag

eorTO

P11

16

27

11

70

34

11

Concealed

preg

nan

cy4

26

21

18

3

Notkn

own

35

84

113

Total

18

23

41

12

255

Atte

ndance

Reg

ular

73

109

182

71

28

6216

68

Missed

1–3

911

20

84

024

8

Missed

4ormore

510

15

65

121

7

Notkn

own

11

21

03

Total

88

131

219

38

7264

Gesta

tionatbooking

<12weeks

42

76

118

47

16

5139

46

12–1

9weeks

35

40

75

30

14

291

30

20+weeks

69

15

61

016

5

Notkn

own

56

11

70

18

Total

88

131

219

38

7264

All

107

154

261

100

50

9320

100

Lewis

38

ª2011Cen

treforMatern

alan

dChild

Enquiries

(CMACE),

BJO

G118(Su

ppl.1),1–2

03

substandard care (%)

0 25 50 75 100

6991

6786


Table 8.1. Direct deaths attributed to anaesthesia and rate per100 000 maternities; UK: 1985–2008

Triennium

Direct deaths

attributable

to anaesthesia

Percentage

of Direct deaths Rate 95% CI

1985–87 6 4.3 0.26 0.12-0.58

1988–90 4 2.8 0.17 0.07-0.44

1991–93 8 6.3 0.35 0.18-0.68

1994–96 1 0.7 0.05 0.01-0.26

1997–99 3 2.8 0.14 0.05-0.42

2000–02 6 5.7 0.30 0.14-0.66

2003–05 6 4.5 0.28 0.13-0.62

2006–08 7 6.5 0.31 0.15-0.64

0

2

4

5

7

1987 1990 1993 1996 1999 2002 2005 2008


Deaths directly due to anaesthesia

The women who diedIn this triennium, two women died from failure to ventilatethe lungs, four from postoperative complications and onefrom leucoencephalitis. Two of the seven women were obese.

Failure to ventilate the lungsThere were two deaths as a result of a failure to ventilate thelungs, one after induction of general anaesthesia and onewhen a tracheostomy tube came out in a critical-care ward.

In the first woman, the anaesthetist failed to stop trying tointubate the trachea even though oxygenation was achievedthrough an intubating laryngeal mask airway (ILMA).Failed intubation guidelines1 were followed, to an extent, inthis very stressful situation, but oesophageal intubationthrough the ILMA was not recognised and further hypoxiaoccurred. The woman was coughing but was not allowed towake up, and a second dose of thiopental and a long-actingneuromuscular-blocking drug were given even though theend-expiratory CO2 monitor indicated that the woman’slungs were not being ventilated. Cricothyrotomy was notattempted.

Patients do not die from a ‘failure to intubate’. They dieeither from failure to stop trying to intubate or from undiag-nosed oesophageal intubation.

Bruce Scott 19862

Much of the success that these Confidential Enquiries intoMaternal Deaths have had in reducing Direct deaths fromanaesthesia has been from tackling airway-related deaths.In the 1967–69 triennial report for England and Wales3

there were 32 such deaths. Striving for absence of suchdeaths is achievable, as in 1994–96, but requires continualefforts. Management of failed intubation/ventilation is acore anaesthetic skill that should be rehearsed and assessedregularly.4 The infrequent use of general anaesthesia inobstetrics, and hence the lack of experience, makes thisextremely important.5 In one region of the UK, during a5-year period from 1999 to 2003, there was an incidence offailed tracheal intubation of one in 238 general anaethetics.In half of these women, there was a failure to follow anaccepted protocol for failed tracheal intubation.6 Recentsurveillance of failed tracheal intubation for obstetric gen-eral anaesthesia conducted through the United KingdomObstetric Surveillance System (UKOSS which is discussedin detail in the Introductory Chapter of this Report)between April 2008 and January 2010 identified 51 womenin an estimated 1.4 million maternities, giving an estimatedrate of failed intubation of 36 cases per million maternities(95% CI 27–48 per million maternities [personal commu-nication with UKOSS]).

Human errors and failures in clinical practice are inevita-ble. Strategies and guidelines need to be in place when errorsor failures occur.7 Assessment of nontechnical skills, such assituation awareness, is given high priority in the aviationindustry but is also very important in medical practice. Inanaesthesia, one must always consider the worst-case sce-nario, implement drills and be aware of what may happenunder stress. An anaesthetist may perceive failed intubationas failed performance, which creates pressure to persist.There is the added fear of acid aspiration, but the impor-tance of maternal oxygenation cannot be overemphasised.

In managing a rare critical situation, it is important to beprepared to implement an accepted drill fully and to main-tain priorities. Drills should not be complex and must bepracticed regularly. The anaesthetist must avoid blind alleysand the natural behaviour patterns of fixation and denial.

It is also pertinent to note that the woman discussedabove had a working epidural in labour when it was decidedto perform a Category 2 caesarean section. Subsequentlythere was a sustained fetal bradycardia, which escalated theurgency of caesarean section to Category 1. The epiduralhad not been topped up to provide surgical anaesthesia forcaesarean section because the anaesthetist planned to topthe epidural up in theatre. If the epidural had been toppedup when it was decided she was to have a caesarean section,general anaesthesia may not have been required.

Epidural anaesthesia for operativedelivery: learning points

Epidural analgesia that has been working well in labourshould be topped up to provide full surgical anaesthesiawithout delay once the decision for operational deliveryhas been made. If the woman cannot be immediatelytransferred to an operating theatre and full epiduralanaesthesia is established on the labour ward, the anaes-thetist and full resuscitation equipment should be imme-diately available and full ‘epidural monitoring’ provided.

A second woman died in a critical-care unit from loss ofthe airway when her tracheostomy tube came out whilebeing turned. She had a known airway problem and knowndifficulty with her tracheostomy.

A clear strategy of management for this scenario wasrequired in advance, including the use of small trachealtubes and quick referral for senior help out of hours.Autopsy revealed a very small larynx and lobular brown tis-sue obscured the tracheostomy orifice.

In these two cases, non-consultant anaesthetists wereexposed to rare emergencies without immediate seniorbackup. Inexperience of rare situations is difficult to

Chapter 8: Anaesthesia



Deaths directly due to anaesthesia

The women who diedIn this triennium, two women died from failure to ventilatethe lungs, four from postoperative complications and onefrom leucoencephalitis. Two of the seven women were obese.

Failure to ventilate the lungsThere were two deaths as a result of a failure to ventilate thelungs, one after induction of general anaesthesia and onewhen a tracheostomy tube came out in a critical-care ward.

In the first woman, the anaesthetist failed to stop trying tointubate the trachea even though oxygenation was achievedthrough an intubating laryngeal mask airway (ILMA).Failed intubation guidelines1 were followed, to an extent, inthis very stressful situation, but oesophageal intubationthrough the ILMA was not recognised and further hypoxiaoccurred. The woman was coughing but was not allowed towake up, and a second dose of thiopental and a long-actingneuromuscular-blocking drug were given even though theend-expiratory CO2 monitor indicated that the woman’slungs were not being ventilated. Cricothyrotomy was notattempted.

Patients do not die from a ‘failure to intubate’. They dieeither from failure to stop trying to intubate or from undiag-nosed oesophageal intubation.

Bruce Scott 19862

Much of the success that these Confidential Enquiries intoMaternal Deaths have had in reducing Direct deaths fromanaesthesia has been from tackling airway-related deaths.In the 1967–69 triennial report for England and Wales3

there were 32 such deaths. Striving for absence of suchdeaths is achievable, as in 1994–96, but requires continualefforts. Management of failed intubation/ventilation is acore anaesthetic skill that should be rehearsed and assessedregularly.4 The infrequent use of general anaesthesia inobstetrics, and hence the lack of experience, makes thisextremely important.5 In one region of the UK, during a5-year period from 1999 to 2003, there was an incidence offailed tracheal intubation of one in 238 general anaethetics.In half of these women, there was a failure to follow anaccepted protocol for failed tracheal intubation.6 Recentsurveillance of failed tracheal intubation for obstetric gen-eral anaesthesia conducted through the United KingdomObstetric Surveillance System (UKOSS which is discussedin detail in the Introductory Chapter of this Report)between April 2008 and January 2010 identified 51 womenin an estimated 1.4 million maternities, giving an estimatedrate of failed intubation of 36 cases per million maternities(95% CI 27–48 per million maternities [personal commu-nication with UKOSS]).

Human errors and failures in clinical practice are inevita-ble. Strategies and guidelines need to be in place when errorsor failures occur.7 Assessment of nontechnical skills, such assituation awareness, is given high priority in the aviationindustry but is also very important in medical practice. Inanaesthesia, one must always consider the worst-case sce-nario, implement drills and be aware of what may happenunder stress. An anaesthetist may perceive failed intubationas failed performance, which creates pressure to persist.There is the added fear of acid aspiration, but the impor-tance of maternal oxygenation cannot be overemphasised.

In managing a rare critical situation, it is important to beprepared to implement an accepted drill fully and to main-tain priorities. Drills should not be complex and must bepracticed regularly. The anaesthetist must avoid blind alleysand the natural behaviour patterns of fixation and denial.

It is also pertinent to note that the woman discussedabove had a working epidural in labour when it was decidedto perform a Category 2 caesarean section. Subsequentlythere was a sustained fetal bradycardia, which escalated theurgency of caesarean section to Category 1. The epiduralhad not been topped up to provide surgical anaesthesia forcaesarean section because the anaesthetist planned to topthe epidural up in theatre. If the epidural had been toppedup when it was decided she was to have a caesarean section,general anaesthesia may not have been required.

Epidural anaesthesia for operativedelivery: learning points

Epidural analgesia that has been working well in labourshould be topped up to provide full surgical anaesthesiawithout delay once the decision for operational deliveryhas been made. If the woman cannot be immediatelytransferred to an operating theatre and full epiduralanaesthesia is established on the labour ward, the anaes-thetist and full resuscitation equipment should be imme-diately available and full ‘epidural monitoring’ provided.

A second woman died in a critical-care unit from loss ofthe airway when her tracheostomy tube came out whilebeing turned. She had a known airway problem and knowndifficulty with her tracheostomy.

A clear strategy of management for this scenario wasrequired in advance, including the use of small trachealtubes and quick referral for senior help out of hours.Autopsy revealed a very small larynx and lobular brown tis-sue obscured the tracheostomy orifice.

In these two cases, non-consultant anaesthetists wereexposed to rare emergencies without immediate seniorbackup. Inexperience of rare situations is difficult to




address, but protocols, drills and simulated practice areknown to help.

Postoperative complicationsFour women died after complications in the postoperativeperiod. One death was related to opiate toxicity in a womanreceiving patient-controlled analgesia but the patient-con-trolled analgesia machine, the syringe and its contents werenot retained for inspection and analysis. A second deathfrom acute circulatory failure, may have been the result ofblood incompatibility after a blood transfusion. Anotherwoman died from cardiac arrest while recovering from gen-eral anaesthesia for a surgical abortion. After the event, ittranspired that the woman was a regular substance abuser.She had been given Syntometrine! intravenously, whichmay have caused the cardiac arrest in a woman with cardiacirritability secondary to substance abuse.

Serious incidents: learning points

When a serious incident occurs, all equipment anddrugs should be retained in situ for inspection and anal-ysis until the cause of the incident is determined.

The fourth woman probably aspirated gastric contents onemergence from general anaesthesia after an emergencycaesarean section. She was considered to need a Category 1caesarean section because of antepartum haemorrhage from aknown placenta praevia, but the bleeding had settled and shewas cardiovascularly stable. She had eaten a full meal in hos-pital before the decision for a Category 1 caesarean section.

General anaesthesia was a reasonable choice, but there wasno documented discussion about whether a Category 1 cae-sarean section was actually indicated or time be allowed forthe stomach to empty. Management of extubation may becritical in the presence of a full stomach. The obstetricpatient should be fully awake and able to protect her air-way before extubation. The stomach was presumed to con-tain gastric contents, and it had not been decompressedwith a wide-bore orogastric tube.8

Full stomach: learning points

When general anaesthesia is administered to a womanwith a potentially full stomach, she should be fullyawake and able to protect her airway before extubation.When a woman is known to have a full stomach, reduc-ing the gastric volume and pressure by gentle ‘in andout’ insertion of a wide-bore orogastric tube before tra-cheal extubation should be considered.

Leucoencephalitis

Acute haemorrhagic disseminated leucoencephalitis wasfound at autopsy in a woman who died some days after anuneventful spinal anaesthetic for caesarean section. Autopsyalso revealed an empyema in the spinal canal covering thelumbar and lower thoracic spinal cord.

Acute haemorrhagic leucoencephalitis, or Hurst’s disease, isa very rare hyperacute and usually fatal form of acutedisseminated encephalomyelitis. The cause is unclear, but itmay be triggered by vaccination or infection. An autoim-mune pathology is likely, with immune cross-reactivitybetween myelin and infectious agent antigens. It was con-sidered that the spinal empyema triggered this very rareautoimmune disease. Although recognising that this was anidiosyncratic disease, it emphasises the necessity for strictasepsis when performing spinal or epidural anaesthesia.

Substandard careThe assessors considered that there was substandard anaes-thetic or perioperative care in six of the seven (86%) Directanaesthetic deaths. Three had major and three had minorsubstandard care as defined in Chapter 1. Although sub-standard care may have been judged as present, it does notnecessarily mean that it caused the death. The cases illus-trate the need for working as part of a team and that allprofessionals should understand the risks of anaesthesia.

PathologyFour deaths attributed to anaesthesia have been reviewed:two related to establishing or maintaining the airway, oneto aspiration and one to opiate toxicity. The detailedautopsy on the death from aspiration showed a failure ofthe autopsy to address the clinical issues:

Inhalation of gastric contents on emergence from generalanaesthesia in a nonstarved woman was suspected, withacute respiratory distress syndrome developing, leading todeath days later. The autopsy was very detailed and histol-ogy was extensive, but there was no mention of a search forinhaled gastric contents.

Deaths to which anaesthesia contributedThere were 18 further Direct or Indirect maternal deaths towhich perioperative anaesthetic management contributedor from which lessons can be learned. These deaths arecounted in the relevant chapters in this Report and dis-cussed here in the categories listed in Table 8.2.

Failure to recognise serious acute illnessYoung, fit, pregnant women have significant physiologicalreserve, which disguises the early warning signs of illness.When a pathological process such as sepsis becomes over-

McClure, Cooper

104 ª 2011 Centre for Maternal and Child Enquiries (CMACE), BJOG 118 (Suppl. 1), 1–203


Table 8.2. Categories under which Direct and Indirect deathsattributed to anaesthesia are discussed

Number*

Anaesthesia was a contributory factor or lesson to be

learned

Failure to recognise serious illness 10

Poor management of pre-eclampsia/eclampsia 8

Poor management of sepsis 6

Poor management of postpartum haemorrhage 5

Poor management of haemorrhage in early pregnancy 5

Others

Failure to consult with an anaesthetist or critical-care

specialist early

12

Obesity BMI >30 kg/m2 9

Anaphylaxis 1

Thromboprophylaxis 1

*Some deaths had more than one contributory factor.


Chronic illness or co-morbidityPregnancy and childbirth are promoted as normal events,but maternity services are increasingly seeing older womenwith significant co-morbidity becoming pregnant. Theassessors for this triennium saw many examples of goodcare of such women where they had been referred to high-risk multidisciplinary and anaesthetic clinics early, forexample:

A woman who had a heart transplant was successfullydelivered by caesarean section under general anaesthesia ina cardiac theatre by a multidisciplinary team with fullmonitoring and inotropic support. Unfortunately, she diedof vascular rejection some weeks after delivery.

However, there were also examples of lack of forwardplanning:

A woman with severe liver disease had an emergency cae-sarean section in her local maternity unit under generalanaesthesia early in her third trimester because of fetaldistress. She was admitted to a critical-care bed postpar-tum but collapsed a few days after delivery because ofintra-abdominal bleeding. She continued to bleed and waseventually transferred to a specialist liver unit but diedthere.

This high-risk woman required full multidisciplinarycare from the outset and should have been delivered in amaternity unit able to provide specialist liver advice andmanagement. This is a lesson that again needs to be high-lighted.

Failure to consult with an anaesthetist or critical-care spe-cialist earlyThere were 12 deaths where referral to an anaesthetist or acritical-care specialist happened too late and supportiveorgan therapy was delayed. Anaesthetists were often notinformed of women admitted with significant pre-eclamp-sia or sepsis because trainees in obstetrics and gynaecologydid not appreciate how ill they were.

Formal consultations from critical-care specialists shouldbe encouraged before critical care is actually required.There was evidence that in consultant-led obstetric andgynaecology services without on-site critical-care beds,there was delay in receiving advice and on-site help fromcritical-care specialists.

ObesityVenous cannulation of the morbidly obese may present achallenge and should not be undertaken by those with littleexperience because of the risk of failure and making subse-quent attempts much more difficult. Familiarity with spe-cial beds for the morbidly obese is necessary in case a

woman needs to be laid flat for resuscitation. The Centrefor Maternal and Child Enquiries and the Royal College ofObstetricians and Gynaecologists have recently publishedclinical guidelines for the management of obese women inpregnancy and childbirth.10

Anaphylaxis

A woman died after suffering an unexpected acute anaphy-lactic reaction to an antibiotic given during labour. She wasnot known to be allergic before this.

The failure to initiate perimortem caesarean section on thelabour ward within 4 minutes of cardiac arrest to deliverthe fetus, may have contributed to the unsuccessful mater-nal resuscitation.11 Acute anaphylaxis requires an immedi-ate medical response including treatment with adrenaline.A formal anaphylaxis protocol,12 similar to a cardiopulmo-nary resuscitation chart, should be immediately availablefor all clinical staff to follow. These charts are already avail-able in every operating theatre.13

Anaphylaxis: learning point

Acute anaphylaxis management charts should be imme-diately available in all clinical areas.

Thromboprophylaxis

A woman had an uneventful emergency caesarean sectionunder epidural anaesthesia but died from a pulmonaryembolism a few weeks later. Thromboprophylaxis wasgiven in too low a dose and was started too late. Theremoval of the epidural catheter was inexplicably delayed,resulting in a subsequent delay in initiating thrombo-prophylaxis. This may have been contributory in thishigh-risk woman.

Thromboprophylaxis guidelines after caesarean section14

recommend the first dose of low-molecular-weight heparin(LMWH) be given 4 hours after spinal or epidural anaes-thesia is established or after removal of an epidural catheterto reduce the risk of a spinal canal haematoma. Epiduralcatheter removal should be timed to avoid delay in givingLMWH. If the epidural catheter is to remain in situ for fur-ther potential surgery or postpartum analgesia, it should beremoved 12 hours after a dose of LMWH and 4 hoursbefore the next dose.

The first dose of LMWH should not be delayed withoutgood reason, e.g. coagulopathy, high risk of postpartumhaemorrhage or a traumatic, bloody epidural/spinal proce-dure.



Chronic illness or co-morbidityPregnancy and childbirth are promoted as normal events,but maternity services are increasingly seeing older womenwith significant co-morbidity becoming pregnant. Theassessors for this triennium saw many examples of goodcare of such women where they had been referred to high-risk multidisciplinary and anaesthetic clinics early, forexample:

A woman who had a heart transplant was successfullydelivered by caesarean section under general anaesthesia ina cardiac theatre by a multidisciplinary team with fullmonitoring and inotropic support. Unfortunately, she diedof vascular rejection some weeks after delivery.

However, there were also examples of lack of forwardplanning:

A woman with severe liver disease had an emergency cae-sarean section in her local maternity unit under generalanaesthesia early in her third trimester because of fetaldistress. She was admitted to a critical-care bed postpar-tum but collapsed a few days after delivery because ofintra-abdominal bleeding. She continued to bleed and waseventually transferred to a specialist liver unit but diedthere.

This high-risk woman required full multidisciplinarycare from the outset and should have been delivered in amaternity unit able to provide specialist liver advice andmanagement. This is a lesson that again needs to be high-lighted.

Failure to consult with an anaesthetist or critical-care spe-cialist earlyThere were 12 deaths where referral to an anaesthetist or acritical-care specialist happened too late and supportiveorgan therapy was delayed. Anaesthetists were often notinformed of women admitted with significant pre-eclamp-sia or sepsis because trainees in obstetrics and gynaecologydid not appreciate how ill they were.

Formal consultations from critical-care specialists shouldbe encouraged before critical care is actually required.There was evidence that in consultant-led obstetric andgynaecology services without on-site critical-care beds,there was delay in receiving advice and on-site help fromcritical-care specialists.

ObesityVenous cannulation of the morbidly obese may present achallenge and should not be undertaken by those with littleexperience because of the risk of failure and making subse-quent attempts much more difficult. Familiarity with spe-cial beds for the morbidly obese is necessary in case a

woman needs to be laid flat for resuscitation. The Centrefor Maternal and Child Enquiries and the Royal College ofObstetricians and Gynaecologists have recently publishedclinical guidelines for the management of obese women inpregnancy and childbirth.10

Anaphylaxis

A woman died after suffering an unexpected acute anaphy-lactic reaction to an antibiotic given during labour. She wasnot known to be allergic before this.

The failure to initiate perimortem caesarean section on thelabour ward within 4 minutes of cardiac arrest to deliverthe fetus, may have contributed to the unsuccessful mater-nal resuscitation.11 Acute anaphylaxis requires an immedi-ate medical response including treatment with adrenaline.A formal anaphylaxis protocol,12 similar to a cardiopulmo-nary resuscitation chart, should be immediately availablefor all clinical staff to follow. These charts are already avail-able in every operating theatre.13

Anaphylaxis: learning point

Acute anaphylaxis management charts should be imme-diately available in all clinical areas.

Thromboprophylaxis

A woman had an uneventful emergency caesarean sectionunder epidural anaesthesia but died from a pulmonaryembolism a few weeks later. Thromboprophylaxis wasgiven in too low a dose and was started too late. Theremoval of the epidural catheter was inexplicably delayed,resulting in a subsequent delay in initiating thrombo-prophylaxis. This may have been contributory in thishigh-risk woman.

Thromboprophylaxis guidelines after caesarean section14

recommend the first dose of low-molecular-weight heparin(LMWH) be given 4 hours after spinal or epidural anaes-thesia is established or after removal of an epidural catheterto reduce the risk of a spinal canal haematoma. Epiduralcatheter removal should be timed to avoid delay in givingLMWH. If the epidural catheter is to remain in situ for fur-ther potential surgery or postpartum analgesia, it should beremoved 12 hours after a dose of LMWH and 4 hoursbefore the next dose.

The first dose of LMWH should not be delayed withoutgood reason, e.g. coagulopathy, high risk of postpartumhaemorrhage or a traumatic, bloody epidural/spinal proce-dure.




pharmacological treatmentoxytocin bolus 5 U i.v. (fractionated),

10-20 U/2h i.v.sulprostone (PgE2) 100-500 µg/h i.v. misoprostol (PgE1) 1000 µg rectallymethylergometrine 0.2 mg

intramyometrically or i.m.

hold uterus, massage (tonus)uterine curettage (tissue)repair laceration (trauma)Bakri-balloon (optional)

mechanical treatment

hemostatic treatment

surgical treatment / explorative laparotomy

compressive stitches(e.g. B-Lynch suture)ligation of uterine or internal iliac arteries

hysterectomy

interventional radiology

if available:uterine artery embolisation

12.10.2009

platelets > 50•109/l, fibrinogen > 1g/l, PT > 50%, pH ≥ 7.2, temp ≥ 35°Replace coagulation factors (consult hemostasiologist if possible)

obstetric evaluation: 4 T's(tonus, tissue, trauma, thrombin)

postpartum hemorrhage (PPH)

unexpected

volume therapy(RL, HES)


if available: cell salvage(leucocyte filter)

expected

rFVIIa

only if all above parameters of hemostatic treatment fullfilled !

40-60-(90) µg/kg

venous accessexpand number and size

accordingly

baseline lab*, T/S*prothrombin time (Quick, INR), activated partial

thromboplastin time (aPTT), fibrinogen, thrombin time;

if available: thromboelastography (ROTEM)

tranexamic acid (1g)consider:donor blood,fibrinogen (2 g) FFP (10-15 ml/kg) platelets



pharmacological treatmentoxytocin bolus 5 U i.v. (fractionated),

10-20 U/2h i.v.sulprostone (PgE2) 100-500 µg/h i.v. misoprostol (PgE1) 1000 µg rectallymethylergometrine 0.2 mg

intramyometrically or i.m.

hold uterus, massage (tonus)uterine curettage (tissue)repair laceration (trauma)Bakri-balloon (optional)

mechanical treatment

hemostatic treatment

surgical treatment / explorative laparotomy

compressive stitches(e.g. B-Lynch suture)ligation of uterine or internal iliac arteries

hysterectomy

interventional radiology

if available:uterine artery embolisation

12.10.2009

platelets > 50•109/l, fibrinogen > 1g/l, PT > 50%, pH ≥ 7.2, temp ≥ 35°Replace coagulation factors (consult hemostasiologist if possible)

obstetric evaluation: 4 T's(tonus, tissue, trauma, thrombin)

postpartum hemorrhage (PPH)

unexpected



if available: cell salvage(leucocyte filter)

expected

rFVIIa

only if all above parameters of hemostatic treatment fullfilled !

40-60-(90) µg/kg

venous accessexpand number and size

accordingly

baseline lab*, T/S*prothrombin time (Quick, INR), activated partial

thromboplastin time (aPTT), fibrinogen, thrombin time;

if available: thromboelastography (ROTEM)




Articles

www.thelancet.com Published online June 15, 2010 DOI:10.1016/S0140-6736(10)60835-5 1

Published OnlineJune 15, 2010 DOI:10.1016/S0140-6736(10)60835-5

See Online/CommentDOI:10.1016/S0140-6736(10)60939-7

*Members listed at end of paper

Correspondence to:Clinical Trials Unit, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, [email protected]

E ects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with signifi cant haemorrhage (CRASH-2): a randomised, placebo-controlled trialCRASH- trial collaborators*

Summary Background Tranexamic acid can reduce bleeding in patients undergoing elective surgery. We assessed the e ects of early administration of a short course of tranexamic acid on death, vascular occlusive events, and the receipt of blood transfusion in trauma patients.

Methods This randomised controlled trial was undertaken in 274 hospitals in 40 countries. 20 211 adult trauma patients with, or at risk of, signifi cant bleeding were randomly assigned within 8 h of injury to either tranexamic acid (loading dose 1 g over 10 min then infusion of 1 g over 8 h) or matching placebo. Randomisation was balanced by centre, with an allocation sequence based on a block size of eight, generated with a computer random number generator. Both participants and study sta (site investigators and trial coordinating centre sta ) were masked to treatment allocation. The primary outcome was death in hospital within 4 weeks of injury, and was described with the following categories: bleeding, vascular occlusion (myocardial infarction, stroke and pulmonary embolism), multiorgan failure, head injury, and other. All analyses were by intention to treat. This study is registered as ISRCTN86750102, Clinicaltrials.gov NCT00375258, and South African Clinical Trial Register D O H -27-0607-1919.

Findings 10 096 patients were allocated to tranexamic acid and 10 115 to placebo, of whom 10 060 and 10 067, respectively, were analysed. All-cause mortality was signifi cantly reduced with tranexamic acid (1463 [14 ·5%] tranexamic acid group vs 1613 [16 ·0%] placebo group; relative risk 0 ·91, 95% CI 0 ·85–0 ·97; p=0 ·0035). The risk of death due to bleeding was signifi cantly reduced (489 [4 ·9%] vs 574 [5 ·7%]; relative risk 0 ·85, 95% CI 0 ·76–0 ·96; p=0 ·0077).

Interpretation Tranexamic acid safely reduced the risk of death in bleeding trauma patients in this study. On the basis of these results, tranexamic acid should be considered for use in bleeding trauma patients.

Funding UK NI H R Health Technology Assessment programme, Pfi zer, BUPA Foundation, and J P Moulton Charitable Foundation.

IntroductionInjuries are major causes of death worldwide.1,2 Every year, more than a million people die as a result of road tra c injuries around the world. Road tra c injuries are the ninth leading cause of death globally, and such injuries are predicted to become the third leading cause of death and disability by 2020. About 1·6 million people die as a result of intentional acts of interpersonal, collective, or self-directed violence every year. More than 90% of trauma deaths occur in low-income and middle-income countries.2 Haemorrhage is responsible for about a third of in-hospital trauma deaths and can also contribute to deaths from multiorgan failure.3

The haemostatic system helps to maintain circulation after severe vascular injury, whether traumatic or surgical in origin.4 Major surgery and trauma trigger similar haemostatic responses, and in both situations severe blood loss presents an extreme challenge to the coagulation system. Part of the response to surgery and trauma is stimulation of clot breakdown (fi brinolysis), which might become pathological (hyper-fi brinolysis) in

some cases.4 Antifi brinolytic agents reduce blood loss in patients with both normal and exaggerated fi brinolytic responses to surgery, and do so without apparently increasing the risk of postoperative complications.5

Tranexamic acid is a synthetic derivative of the aminoacid lysine that inhibits fi brinolysis by blocking the lysine binding sites on plasminogen.6 A systematic review of the randomised trials of tranexamic acid in patients under-going elective surgery identifi ed 53 studies including 3836 participants.5 Tranexamic acid reduced the need for blood transfusion by a third (relative risk [RR] 0·61, 95% CI 0·54–0·70), with no signifi cant reduction in mortality (0·61, 0·32–1·12).5 Because the haemostatic responses to surgery and trauma are similar,4 tranexamic acid might reduce mortality due to bleeding in trauma patients. However, up until now there have been no randomised trials of this drug in such patients.7 We assessed the e ects of the early administration of a short course of tranexamic acid on death, vascular occlusive events, and the receipt of blood transfusion in trauma patients with or at risk of signifi cant haemorrhage.

Lancet. 2010 Jul 3;376(9734):23-32

20’211


Anaesthesia informed

Epidural in situ (2 attempts)

strong vaginal bleeding

CS under epidural anesthesia


Anesthesia-RelatedMaternal MortalityJOY L. HAWKINS, MDUniversity of Colorado School of Medicine

Maternal Mortality in theUnited StatesThis year the Centers for Disease Controland Prevention (CDC) published their dataon maternal mortality from 1991 to 1999.1,2

They note that although death from compli-cations of pregnancy have decreased by99% since 1900, there have been no furtherdecreases in the last 2 decades. In the mostrecent report, there were 4200 pregnancy-related deaths with an overall mortality ratioof 11.8 deaths per 100,000 live births, a sub-stantial increase from the 7 to 8 per 100,000reported since 1982. The appearance of anincrease is probably just due to better meth-ods of ascertainment, but it is still far fromthe Healthy People 2010 objective for ma-ternal mortality of 3.3 per 100,000 livebirths! Those at greatest risk were women ofblack race, women >34 years of age, andwomen who received no prenatal care.Among women who died after a live birth,the leading causes of death were embolismand pregnancy-induced hypertension.

A maternal death is devastating to all in-volved; after all, only in the obstetric patientcan mortality be 200%! Although infantmortality has declined steadily due to in-

creased survival of preterm infants and pre-vention of Sudden Infant Death Syndrome(SIDS), maternal mortality has remained ap-proximately 7.5 maternal deaths per100,000 live births over the last 15 years, un-til the most recent report mentionedabove.1–3 The reason for the lack of im-provement is unclear. More than half of ma-ternal deaths are preventable—hemorrhage,pregnancy-induced hypertension, infection,and ectopic pregnancy account for 59%. An-esthetic causes have fallen to a “respectable”#7 on the list of causes for maternal mortal-ity in the United States. The causes of preg-nancy-related deaths are shown in Ta-ble 1.1,4

Since about 1991, the United States Cen-ters for Disease Control (CDC) define ma-ternal deaths as those that occur within 1year of delivery (rather than the 42 days usedpreviously) and that are related to the preg-nancy. Thus, the percentage of deaths due tocardiomyopathy, for example, has increasedbecause those deaths often occur after alengthy illness. Many maternal deaths (per-haps over 30%) are missed because thecause of death on the death certificate doesnot include the fact that the mother waspregnant. For example, if a woman dies of apulmonary embolism, but the death certifi-cate does not note she was pregnant, it wouldnot be classified as a maternal death. The

Correspondence: 4200 East Ninth Avenue, B-113 Den-ver, CO 80262, E-mail: [email protected]

CLINICAL OBSTETRICS AND GYNECOLOGYVolume 46, Number 3, 679–687© 2003, Lippincott Williams & Wilkins, Inc.

CLINICAL OBSTETRICS AND GYNECOLOGY / VOLUME 46 / NUMBER 3 / SEPTEMBER 2003

679

vacaine and probably due to increasingawareness of local anesthetic toxicity andincreased use of test dosing. Using the num-ber of deaths in each 6-year period, and es-timating the number of cesarean deliveriesdone under regional or general anesthesiaeach year (note there are more and more cal-culations and assumptions), case fatalityrates and risk ratios could be calculated.

Although the results may not be entirelyaccurate because of all the missing data andassumptions involved, they do show thatgeneral anesthesia is riskier than regionalanesthesia in the obstetric patient. Whyshould that be?

1. During general anesthesia the airway must al-ways be managed, and airway management ismore difficult in the obstetric patient. Airwayproblems were by far the most common causeof anesthesia-related deaths.

2. General anesthesia is often chosen in emer-gencies when preparation and examination ofthe patient is not optimal.

3. General anesthesia is used in patients whohave failed regional anesthesia (eg, obesity)or have contraindications to its use dueto medical conditions (eg, hemorrhage,HELLP). These patients often also have in-creased risk factors for a difficult airway.

4. Residency training programs may not provideresidents adequate exposure to general anes-thesia on their obstetric rotations because an-esthesiologists, patients, and obstetriciansprefer regional anesthesia.

A review performed at a large tertiarycare obstetric facility found general anesthe-sia was used in only about 5% of cesareandeliveries between 1990 and 1995.9 The in-

dications for cesarean delivery in patientsreceiving general anesthesia were nonreas-suring fetal heart tracing, placenta previa orabruption, maternal disease (primarilyHELLP, preeclampsia or ITP), abnormalpresentation, and cord prolapse. Theiryearly incidence of difficult intubationranged from 1.3 to 16.3% with 1 maternalmortality due to an unrecognized difficultairway.

How do anesthesiologists in practicemaintain their skills in general anesthesia forcesarean delivery with such infrequent use?Consider an anesthesiologist practicing at ahospital with 1500 deliveries per year.8 Ifthe cesarean delivery rate is 20%, there willbe 300 cases, and if 12% are done using gen-eral anesthesia there will be 36 such casesper year. With 6 practitioners in the group,each will do an average of only 1 generalanesthetic for cesarean delivery every othermonth!

It would appear that maternal mortalitywill decrease further only by continuing toincrease use of regional anesthesia and pro-viding organized airway management pro-grams for residents and practitioners so theyare prepared for obstetric airway emergen-cies.9 Even deaths during regional anesthe-sia may involve airway management. Sev-eral of the deaths during regional anesthesiaoccurred when the block became too highfor adequate ventilation and the airwaycould not be secured, leading to hypoxiaand/or aspiration.

However, there are times when generalanesthesia is the most appropriate choice for

TABLE 3. Numbers of Anesthesia-Related Deaths, Case Fatality Rates, and Risk Ratios (byType of Anesthesia Provided) in the United States, 1979–1996

Year of DeathCase Fatality RatesGeneral Anesthetics*

Case Fatality RatesRegional Anesthetics* Risk Ratios

1979–1984 20.0 8.6 2.31985–1990 32.3 1.9 16.71991–1996 16.8 2.5 6.7

* Per million general or regional anesthetics.

Adapted from References 6 and 7.

Anesthesia-Related Maternal Mortality 681

Clinical Obstetrics and Gynecology 2003; 46(3):679


British Journal of Anaesthesia 95 (5): 706–9 (2005)

doi:10.1093/bja/aei231 Advance Access publication September 2, 2005

Pre-oxygenation in the obese patient: effects of position ontolerance to apnoea

F. R. Altermatt*, H. R. Munoz, A. E. Delfino and L. I. Cortınez

Departamento de Anestesiologıa, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Chile

*Corresponding author. E-mail: [email protected]

Background. In obese patients, reduced functional residual capacity exacerbated by supineposition might decrease the effectiveness of pre-oxygenation and the tolerance to apnoea.The aim of this study was to compare the effect of body posture during pre-oxygenation, sittingor supine, on its effectiveness in obese patients.

Methods. Forty obese patients (BMI >35 kg m!2) undergoing surgery with general anaesthesiawere randomly assigned to one of two groups: Group 1 (sitting, n=20) or Group 2 (supine, n=20).In the predetermined body position, pre-oxygenation was achieved with eight deep breaths within60 s and an oxygen flow of 10 litre min!1. After rapid sequence induction of anaesthesia indecubitus position, the trachea was intubated and the patient was left apneic and disconnectedfrom the anaesthesia circuit until SpO2

decreased to 90%. The time taken for desaturation to90% from the end of induction of anaesthesia was recorded. Arterial blood oxygen tension wasmeasured before (baseline) and after pre-oxygenation. Values were compared with two-wayANOVA and unpaired Student’s t-test.

Results.Oxygen and carbon dioxide tensions were similar between groups, both at baseline andafter pre-oxygenation. However, the mean time to desaturation to 90% was significantly longerin the sitting group compared with the supine group [mean (SD): 214 (28) vs 162 (38) s, P<0.05].

Conclusions. Pre-oxygenation in sitting position significantly extends the tolerance to apnoea inobese patients when compared with the supine position.

Br J Anaesth 2005; 95: 706–9

Keywords: anaesthetic techniques, pre-oxygenation; complications, obesity; position, effects

Accepted for publication: August 1, 2005

Management of obese patients (BMI > 30 kgm!2) representsa challenge for the anaesthetist in many ways, particularlyadequate airway management during induction. A BMIgreater than 26 kg m!2 is a strong predictor of higher riskof difficult ventilation with facemask1 and, arguably,associated with a greater risk of difficult intubation andaccompanying desaturation.2 This setting emphasizes theimportance of an adequate pre-oxygenation to maximizethe period of non-hypoxaemic apnoea that obese patientscan tolerate.

In patients of normal weight, the effectiveness of pre-oxygenation varies with the technique. A forced vitalcapacity ventilation for eight breaths during 60 s withhigh flows of oxygen 100% was shown to achieve adequatedenitrogenation and slower desaturation during apnoeacompared with the usual 3 min tidal-volume ventilationtechnique.3

Obesity, however, affects pulmonary function that canseriously impair the effectiveness of pre-oxygenation; themain reason being a decrease in functional residual capacity

(FRC) secondary to cephalad diaphragmatic displacement.4

Thus, in obese patients desaturation of arterial blood afteronset of apnoea is reached within a significantly shorter timethan in a non-obese patient.5

Since FRC is highly sensitive to changes in bodyposition, being larger in the upright or sitting than in thesupine position,6 we hypothesized that the efficacy of pre-oxygenation in obese patients might be improved by modi-fying the position of the patient during this manoeuvre.Thus, the aim of this study was to compare the effect of

the sitting against the supine position, in obese patients, onthe effectiveness of pre-oxygenation defined as the durationof non-hypoxaemic apnoea.

MethodsAfter institutional Ethics Committee approval, and obtainingwritten informed consent, 40 unpremedicated obesepatients (BMI >35 kg m!2), ASA II or III, undergoingelective surgery with general anaesthesia, were studied.

! The Board of Management and Trustees of the British Journal of Anaesthesia 2005. All rights reserved. For Permissions, please e-mail: [email protected]

at University of Basel / U

niversity Library on February 12, 2011bja.oxfordjournals.org

Dow

nloaded from

SaO2 90%214 vs. 162s



!

!"#$%&'%()$"#*)$#+#,*!-./$+*(0./%12%30$3-++%4$$

)56789:;9<=$>=?$@658$A>=B>C$

!

Contents:

Page 2...................................................... Introduction

Page 3..................................................... Components

Page 4&5................................................. User Instructions

Page 6...................................................... Patient Positioning & Aftercare

Page 7...................................................... Clinical Benefits

Page 8...................................................... Clinical References

!"#$%&'%()$"#*)$#+#,*!-./$+*(0./%12%30$3-++%4$-1$+*!#&$'(##D$&E(*0$!(*.1+@2#.!$*.)$*.!-E1!*!-2$

$

!

2

THE OXFORD HELP Introduction

! !

Compare the difference between pictures A and B. This patient has a BMI of 49.2.In picture A the patient is conventionally positioned. In picture B the patient is now correctly positioned on the Oxford Head Elevating Laryngoscopy Pillow.

The following has happened:

I. The airway axis is better aligned II. The thyromental distance has increased

III. The sniffing position is achieved IV. Cricoid access is improved

This is all completed instantly and the result will be:

a) Improved laryngoscopy b) Enhanced view c) Easy manual ventilation d) Increased FRC and Vt e) Patient comfort is increased f) Comfortable operating position for clinician

!

!

!

!" #"

To achieve the head elevated position you are trying to create an imaginary approximate line from the external auditory meatus or the tragus to the suprasternal notch. This should also improve the patient s thyromental distance.

The Oxford Hpositioning high BMI patients for anaesthesia so that they function, physiologically, like a patient with a normal BMI while still maintaining them in a conventional induction position.

The upper airway anatomy is uniquely realigned.! !

HELP


Anesthesiology 1997;86:778-84


sitting, bend forward

lateral position

4.28 cm


United Kingdom

2010

Maternal obesity in the UK:

Improving the health of mothers, babies and children


12

1.1.7. Clinical care during labour and delivery

12

1.1.8. Postpartum care and follow-up

12


12

Supporting evidence

Rationale

Recommendation 7: Anaesthesia in pregnancy and labour

12

anaesthetic consultation

Timing of epidural !


Supporting evidence

Rationale

21

For these

Recommendation 8: Thromboembolism and thromboprophylaxis


[email protected]


Documents

WHAT’S NEW IN OBSTETRIC ANAESTHESIA · 2018. 6. 11. · Oxytocin-Bolus-Injektion in Dosen von mehreren I.E. eine vorübergehende asymptomatische QT-Arzneimittel-Kompendium der Schweiz