Drug Selection & Dosing in Patients on Extracorporeal ... · PDF filePatients on Extracorporeal Membrane Oxygenation ... Cardiogenic shock ... et al.Pharmacotherapy. 2016;36:607–16

Drug Selection & Dosing in Patients on Extracorporeal

Membrane Oxygenation

Jenna N. Dietr ich, PharmDPGY2 Crit ical Care Pharmacy Resident

Cari l ion Roanoke Memorial Hospital Apri l 7, 2017

I have no actual or potential conflict of interest in relation to this presentation.

Off-label use of medication will be discussed during this presentation.

Disclosure Statement

Discuss the indications for ECMO therapy

Explain different modalities of ECMO support

Identify alterations in pharmacokinetics and pharmacodynamics associated with ECMO

Implement appropriate dose modifications for medications frequently used in critically i l l patients, including antimicrobials, sedatives and analgesics

Learning Objectives

Extracorporeal membrane oxygenation

Type of extracorporeal life support (ECLS)

Temporary support for respiratory and/or cardiorespiratory failure

High-risk, complex therapy considered in patients unresponsive to optimal care

ECMO

Extracorporeal Life Support Organization. ELSO Guidelines for Cardiopulmonary Extracorporeal Life Support. www.elsonet.org

ECMO Circuit

Ha MA, et al. Evaluation of Altered Drug Pharmacokinetics in Critically Ill Adults Receiving Extracorporeal Membrane Oxygenation. Pharmacotherapy. 2017;37(2):222.

Types of ECMO

Shekar, et al. Pharmacokinetic changes in patients receiving extracorporeal membrane oxygenation. J Crit Care. 2012;27:741.e10

Cardiac Failure Card iogen ic shock Acute myocard ia l in fa rc t ion Per ipar tum card iomyopathy Decompensa ted hear t fa i lu re Fu lminan t myocard i t i s Pulmonary hyper tens ion and r igh t hear t

fa i l u re Pulmonary embo lus w i th hemodynamic

compromise Card iac a r res t (ass is ted CPR) Medica t ion overdose Non ischemic card iomyopathy inc lud ing

seps is induced card iomyopathy Suppor t pos t ca rd iac su rgery

Br idge to : Recovery

Acute MI af ter revascular izat ion, myocardi t is, postcardiotomy

Transp lan t Unrevascular izable acute MI, chronic heart fa i lure

Imp lan tab le c i rcu la to ry suppor t VAD, TAH

Respiratory Failure Cons ider when r i sk o f mor ta l i t y >50%

PaO2/F iO2 <150 on F iO2 >90% and/or Murray score 2-3

Ind ica ted when r i sk o f mor ta l i t y >80% PaO2/FiO2 <100 on FiO2 >90% and/or Murray

score 3-4 despi te opt imal care for 6+ hours CO2 re ten t ion desp i te h igh Pp la t (>30) Severe a i r l eak syndromes Immed ia te ca rd iac / resp i ra to ry co l lapse Severe ARDS Sta tus as thmat i cus Br idge to lung t ransp lan ta t ion Post lung t ransp lan ta t ion p r imary g ra f t

fa i l u re Di f fuse a lveo la r hemor rhage Pulmonary hyper tens ive c r i s i s Pulmonary embo l i sm Severe b ronchop leura l f i s tu la

Indications

Combes, et al. Am J Respir Crit Care Med. 2014;190(5):488-96.Extracorporeal Life Support Organization. ELSO Guidelines for Cardiopulmonary Extracorporeal Life Support. www.elsonet.org

Cardiac FailureAbsolute: Unrecoverable heart and not a

candidate for transplant or VAD Advanced age Chronic organ dysfunct ion

(emphysema, cirrhosis, renal fai lure)

Compliance (f inancial, cognit ive, psychiatr ic, or social l imitat ions)

Prolonged CPR without adequate t issue perfusion

Relat ive: Contraindicat ion for

ant icoagulat ion Advanced age Obesity

Respiratory FailureAbsolute: None, consider r isks/benef i ts for

each pat ient indiv idual ly

Relat ive: MV at high settings (FiO2 >90%, P-

plat >30) for 7+ days Major pharmacologic

immunosuppression (ANC<400/mm3)

Recent or expanding CNS hemorrhage

Non-recoverable comorbidi ty (major CNS damage, terminal mal ignancy)

Age

Contraindications

Extracorporeal Life Support Organization. ELSO Guidelines for Cardiopulmonary Extracorporeal Life Support. www.elsonet.org

Bleeding

Thrombosis

Infection

Acute limb ischemia, compartment syndrome

Pulmonary edema

Complications

Lafçı, et al. Heart Lung and Circ. 2014;23:10-23.

ECMO for Cardiac Failure

Design Systematic review of case reports, case-series and case-control studies

N 1494

PatientsPatients with cardiogenic shock or cardiac arrest

Cardiogenic shock: 533 patients; Cardiac arrest: 675 patients; Mixed: 286 patients

Results

Weaned from ECMO:

• All patients: Mean, 76.8 ± 4.2%; Median, 66.0% (IQR 50%, 100%)

Survival to discharge: • All patients: Mean 47.4 ± 4.5%, Median 40.0% (IQR 20%, 75%) • Cardiogenic shock: Mean 51.6 ± 6.5%, Median 38.5% (IQR 23.4%, 76.3%)• Cardiac arrest: Mean 44.9 ± 6.7%; Median 42.3% (IQR 15.4%, 75%)

Nichol G, et al. Resuscitation. 2006; 70(3):381-94.

ECMO for Respiratory Failure

Design RCT

N 90

Patients

Severe acute respiratory failure due to pneumonia, pulmonary embolism, thoracic or severe extra-thoracic trauma, sepsis, inhalation injury, fluid overload/congestive failure

65% of patients had bacterial, viral, aspiration, or interstitial pneumonia7% had posttraumatic ARDS

Average MV time before study entry: 7 vs. 9.6 days in control and ECMO groups, respectively

Results

ECMO group (n=42) vs. Conventional management (n=48)

• Mortality rate: 90% vs. 92%• Mortality rate was 100% for posttraumatic ARDS patients• 7 of 8 surviving patients received no more than 7 days of MV before enrollment

Zapol, et al. JAMA.1979;242(20):2193-6.


Design RCT

N 180

Patients

Severe but reversible respiratory failure due to pneumonia (61%), other ARDS (28%), trauma (7%), and other causes (4%)

Excluded TBI patients and patients requiring high FiO2 ventilation for more than 7 days

Only 76% of patients in the ECMO group actually received ECMO support

ResultsConsideration for ECMO (n=90) vs. Conventional management (n=90)

• 6 month survival without disability: 63% vs. 47% • 6 month survival rate: 63% vs. 50%

Peek, et al. Lancet. 2009;374:1351-63.


Design Retrospective cohort study

N 102

Patients

Trauma patients without an acute intracranial hemorrhage (ICH)65% of patients had bacterial, viral, aspiration, or interstitial pneumonia

7% had posttraumatic ARDS

Average MV time before study entry: 7 vs. 9.6 days in control and ECMO groups, respectively

Results


• Unadjusted survival rate: 58% vs. 55% • Multivariate logistic regression: ECMO independently associated with improved survival• Propensity scores matching for age and P/F ratio compared 2 subgroups of 17 patients

• 60 day survival rate post-injury: was 64.7% vs. 23.5%• Hemorrhagic complications were more frequent in the ECMO group• Pulmonary complications were higher in the conventional ventilation group

Guirand, et al. J Trauma Acute Care Surg. 2014;76(5):1275-81.


Design RCT

N 29

PatientsTrauma patients with severe ARDS refractory to maximal mechanical ventilator supportAverage MV time before ECMO initiation was 7.5 days

Average time between diagnosis of severe ARDS and ECMO initiation was 1.9 days

Results


• Mortality rate: 13.3% vs. 64% (p = 0.01) • No difference in ICU-free days, hospital LOS, and ventilator-free days• Hemorrhagic complications were more frequent in the ECMO group

Bosarge, et al. J Trauma Acute Care Surg. 2016;81:236-43.

Significant PK alterations can occur during ECMO support

Considerable implications for critically i l l patients, especially those with life-threatening infections

Balance toxicity versus the risk of therapeutic failure

Pharmacotherapy Considerations During ECMO

Patient Variables

• Age, weight• Allergies• Comorbidities• ECMO indication• Organ dysfunction,

renal replacement therapy

• Pregnancy

Drug Variables

• Pharmacology• Drug interactions• Toxicity profile

• Pharmacokinetics• Vd

• Physiochemical properties• Lipophilicity• Protein binding• Molecular size• Ionization• Chemical stability

Circuit Variables

• Circuit age, type• Oxygenator• Tubing• Priming

Shekar, et al. J Crit Care. 2012;27:741.Burcham, et al. Ann Transl Med. 2017;5(4):69.

HA, et al. Pharmacotherapy. 2017;37(2):221-35.

Mechanisms of Pharmacokinetic Changes

ECMO-Related Change PK Change Drugs Affected

Hemodilution Vd Cmax Hydrophilic

Drug sequestration Vd Cmax

Lipophilic Highly protein-bound

Drug inactivation CL Chemically unstable

Organ dysfunction CL Vd Renal/hepatic excretion

SIRS CL Vd Cmax

Hydrophilic

Shekar, et al. J Crit Care. 2012;27:741. Shekar, et al. Crit Care. 2015;19:164. Dzierba, et al. Crit Care. 2017;21:66.

Common Pharmacokinetic Alterations

Hydrophilic drugsLow Vd

Renal ClearanceLow log P

Vd (large) Cmax or CL

(dependent on renal function)

Lipophilic drugs

High VdHepatic

ClearanceHigh log P

Vd (minimal) Circuit

sequestration or CL

(dependent on hepatic function)

Shekar, et al. J Crit Care. 2012;27:741. Dzierba, et al. Crit Care. 2017;21:66.


SEDATION & ANALGESIA

Drug Vd (L) LogP Pb (%)

Fentanyl 280-420 4.05 79-87

Morphine 70-350 0.89 20-35

Dexmedetomidine 118 3.39 94

Midazolam 70-217 3.89 97

Propofol 4200 3.79 95-99

Ketamine 140-210 2.9 471Standardized to 70-kg patient


PK & Physiochemical Properties

Ex vivo studies: adult ECMO circuits, composed of PVC tubing +hollow polymethylpentene fiber membrane oxygenator Wagner Dexmedetomidine: 93% loss at 24 h

Shekar Morphine: 103% recovery at 24 h Fentanyl: 70% lost in 1 h; 3% of baseline concentrations at 24 h Midazolam: 50% lost in 1 h; 13% of baseline concentrations at 24 h

Lemaitre Propofol: 30% of baseline concentrations at 30 min; negligible at 24 h Midazolam: 54% of baseline concentrations at 30 min; 11% at 24 h

Sedation & Analgesia: Evidence

.Wagner, et al. Perfusion. 2013;28:40–6. Shekar, et al. Crit Care. 2012;16:R194.

Lemaitre. Crit Care. 2015;19:40.

Case report 30 year old male, on VV ECMO as bridge to lung transplantation Increased morphine and propofol requirements over 19 days of

ECMO support

Single‐center, retrospective study 29 consecutive patients requiring ECMO (13 VV, 16 VA) Average daily dose increase Midazolam: 18 mg (p = 0.001) Morphine: 29 mg (p = 0.02) Fentanyl: No significant increase


.Shekar, et al. Anaesth Intensive Care. 2012;40:1067–9.Shekar, et al. Anaesth Intensive Care. 2012;40:648–55.

Single‐center, prospective cohort study 32 patients on VV or VA ECMO Median daily dose Opioids: 3875 mcg Benzodiazepines: 24 mg

Retrospective cohort study Adult patients with severe respiratory failure with or without VV

ECMO support requiring at least one sedative ECMO (n=34) vs. no ECMO (n=60) Maximum median 6‐hour sedative exposure was almost twice as high in

the ECMO group but no significant difference in the adjusted analyses


.DeGrado, et al. J Crit Care. 2016;37:1–6.

Der Nigoghossian, et al. Pharmacotherapy. 2016;36:607–16.

Randomized trial Standard sedation practices +/- low dose ketamine 20 patients on VV ECMO for severe respiratory failure No differences in opioid or sedative requirements

Ketamine for Adjunct Therapy

Dzierba, et al. Ketamine use in sedation management in patients receiving extracorporeal membrane oxygenation. Intensive Care Med. 2016;42:1822-3.

Fentanyl may require escalating doses; consider alternative agents

Morphine may require dose adjustment; morphine is less l ipophil ic than fentanyl, thus it is a potentially superior option

Dexmedetomidine may require an increased starting dose

Midazolam requires an increased dose; consider alternative agents

Propofol may require an increased dose; consider alternative agents

Insufficient data regarding ketamine dosing

Sedation & Analgesia: Key Findings

.HA, et al. Pharmacotherapy. 2017;37(2):221-35.

Dzierba, et al. Crit Care. 2017;21:66.

Lipophilic agents have a high propensity to be adsorbed or sequestered by the circuit

Upon ECMO initiation, anticipate requirements that exceed standard doses

Anticipate the need for significant dose reductions at the time of ECMO discontinuation

Sedation & Analgesia: Considerations



ANTIMICROBIALS

Drug Vd1 (L) LogP Pb (%)Ampicillin 20-27 0.67 15-28

Cefazolin 35 -0.58 74-86

Ceftriaxone 6-14 -0.01 85-95

Meropenem 15-20 -0.69 2

Piperacillin-tazobactam 17 0.67 30

Vancomycin 28-70 -4.4 50

Aminoglycosides:gentamicin, tobramycin, amikacin 14-21 < 0 < 30

Ciprofloxacin 147-189 2.3 20-40

Levofloxacin 89 0.65 24-38

Moxifloxacin 119-189 0.01 50

Caspofungin 8-10 -2.8 97

Fluconazole 42 0.56 12

Voriconazole 322 2.56 58

Oseltamivir 23-26 1.16 421Standardized to 70-kg patient HA, et al. Pharmacotherapy. 2017;37(2):221-35.

PK & Physiochemical Properties

Ex-vivo study: ECMO circuits composed of sil icone membrane oxygenator Blood-primed circuits 15% drug loss at 24 h

Crystalloid-primed circuits 71% drug loss at 24 h

Ampicillin

Mehta, et al. Intensive Care Med. 2007;33:1018–24.

Ex-vivo study: ECMO circuits composed of sil icone membrane oxygenator Blood-primed circuits 22% drug loss at 24 h

Crystalloid-primed circuits 22% drug loss at 24 h

Cefazolin

Mehta, et al. Intensive Care Med. 2007;33:1018–24.

Ex-vivo study: ECMO circuit composed of centrifugal pumps and polymethylpentene oxygenators Average drug recovery of 80% at 24 h

Ceftriaxone

.

Shekar, et al. Crit Care. 2015;19:164.

Meropenem

Shekar, et al. Altered antibiotic pharmacokinetics during extracorporeal membrane oxygenation: cause for concern? J Antimicrob Chemother. 2013;68:726-7.

Ex vivo study: adult ECMO circuits, composed of PVC tubing + hol low polymethylpentene fiber membrane oxygenator 20% of baseline concentrations at 24 h Stable in the circuit and the controls in the first 120 min; 62% recovered at 6 h

Open-label, descript ive, matched-cohort PK study 11 patients on VV or VA ECMO; 5 patients also on RRT Compared to 10 critically il l patients with sepsis not receiving ECMO (controls) ECMO patients vs. Controls

Volume of distr ibution: 0.45 ± 0.17 vs. 0.41 ± 0.13 L/kg, P=0.21 Clearance: 7.9 ± 5.9 vs. 11.7 ± 6.5 L/h, P=0.18

All ECMO patients achieved trough concentrations >2 mg/L, but only 8 patients achieved a more aggressive target of >8 mg/L for less susceptible microorganisms

Retrospect ive, case‐control study 26 ECMO (VA or VV) patients, 41 matched controls 9 patients also received CRRT 27 TDM results

No differences in PK paramenters High variabil i ty in PK parameters 30% of levels were subtherapeutic

Meropenem

.Shekar, et al. Crit Care. 2012;16:R194.

Shekar, et al. Crit Care. 2014;18:565.Donadello, et al. Int J Antimicrob Agents. 2015;45:278–82.

Retrospective, case‐control study 26 ECMO (VA or VV) patients, 41 matched controls 9 patients also received CRRT 14 TDM results No differences in PK paramenters High variability in PK parameters 30% of levels were subtherapeutic

Piperacillin-Tazobactam

.

Donadello, et al. Beta-lactam pharmacokinetics during extracorporeal membrane oxygenation therapy: A case-control study. Int J Antimicrob Agents. 2015;45:278–82.

Ex vivo studies: adult ECMO circuits, composed of PVC tubing + hollow polymethylpentene fiber membrane oxygenator Lemaitre Concentration remained stable at 48 h

Shekar 90% of baseline concentrations at 24 h

Retrospective matched cohort study Adult critically ill patients +/- ECMO (VA or VV) for cardiogenic

shock, ARDS or sepsis; 7 patients on CRRT 35 mg/kg loading dose over 4 h, followed by continuous infusion ECMO (n=11) vs. Control (n=11) Median AUC (mghr/L): 628 vs. 698 No significant differences in vancomycin levels during the first 24 hours

Vancomycin

.Shekar, et al. Crit Care. 2012;16:R194.Lemaitre, et al. Crit Care. 2015;19:40.

Donadello, et al. Crit Care. 2014;18:632.

Ciprofloxacin Ex-vivo study: ECMO circuit composed of centrifugal pumps and

polymethylpentene oxygenators Average drug recovery of 96% at 24 h

Fluoroquinolones

.

Shekar, et al. Crit Care. 2015;19:164.

PK studies largely limited to the neonatal population

Amikacin Observational study 46 patients on VA or VV ECMO were matched with 50 critically ill

patients without ECMO support (controls) ECMO vs. Controls Cmax (mg/l): 71.7 (58.9–79.7) vs. 68.4 (53.0–81.0) Insufficient Cmax: 13/50 (26%) vs. 17/50 (34%) Excessive Cmax: 12/50 (24%) vs. 15/50 (30%) Cmin above toxic threshold: 28/43 (65%) vs. 30/50 (60%)

Comparable PK in critically ill patients with or without ECMO support

Aminoglycosides

.

Gélisse, et al. Intensive Care Med. 2016;42:946–8.

Linezolid 3 adult patients receiving ECMO May not achieve therapeutic targets with standard dosing when MIC >1 mg/l

Ex-vivo study: ECMO circuit composed of centrifugal pumps and polymethylpentene oxygenators Average drug recovery of 91% at 24 h

Azithromycin PK appears to be similar between ECMO patients and non‐ECMO

critically ill controls

Tigecycline Case study Levels similar to expected levels based on population PK

Other Antimicrobials

.

De Rosa, et al. Int J Antimicrob Agents. 2013;41:590–1.Shekar, et al. Crit Care. 2015;19:164.

Turner, et al. Pharmacother. 2016;50:72–3.Veinstein, et al. J Antimicrob Chemother. 2012;67:1047–8.

Consider alternative agents over ampicil l in

Cefazolin may require a dosage adjustment

Meropenem may require more frequent dosing or higher doses

Vancomycin does not require a dosage adjustment; dosing guided by therapeutic drug monitoring

Insufficient data for aminoglycosides; dosing guided by therapeutic drug monitoring

No dosage adjustment is necessary for ceftriaxone, piperacil l in-tazobactam, or f luoroquinolones

Antimicrobials: Key Findings

Fluconazole Ex-vivo study: ECMO circuit composed of centrifugal pumps and


Voriconazole Ex-vivo study: ECMO circuits composed of silicone membrane oxygenator 71% drug loss at 24 h

Caspofungin Ex-vivo study: ECMO circuit composed of centrifugal pumps and


Case report No significant differences in peak concentrations or Vd for a patient during

ECMO when compared to adult references Case report Low to undetectable caspofungin concentrations in a patient receiving ECMO

Antifungals: Studies

Shekar, et al. Crit Care. 2015;19:164.Mehta, et al. Intensive Care Med. 2007;33:1018–24.

Spriet, et al. J Antimicrob Chemother. 2009;63:767–70.Ruiz, et al. Intensive Care Med. 2009. 35:183–184

Insufficient data for fluconazole; increased loading dose may be required; maintenance doses may not require adjustment

Voriconazole concentrations appear to be significantly affected Increased loading dose required (100% increase) Daily therapeutic drug monitoring recommended to monitor for

circuit saturation

Insufficient data for caspofungin; dosage adjustment may be required

Antifungals: Key Findings

PK study Intervention: oseltamivir 75 or 150 mg twice daily 7 patients on VV ECMO for severe pandemic (H1N1) influenza associated with ARDS +/-

CVVHDF for renal failure Results: ECMO + CVVHDF (n=3) vs. ECMO (n=4)

Cmax (ng/mL) OC, mean (range): 4173 (3944–4551) vs. 1029 (349–1470) AUC (ng•h/mL) OC, mean (range): 42,730 (39,200–49,400) vs. 9,000 (2,200–14,500)

Prospect ive, open- label , PK study Intervention: oseltamivir 150 mg twice daily 12 patients on CVVHD +/- ECMO, with suspected or confirmed H1N1 influenza Results: ECMO + CVVHD (n=4) vs. CVVHD (n=8)

Cmax (ng/ml) OC, median (IQR): 981 (553–1670) vs. 2670 (1710–3580) AUC (ng•hr/ml) OC, median (IQR): 9390 (5000–17,600) vs. 29,500 (17,600–35,800) No substantial di f ferences between preoxygenator and postoxygenator serum concentrations

PK study Intervention: oseltamivir 75 mg twice daily 14 ECMO, 4 patients also on CVVH ECMO (n=14) vs. healthy adult references

Cmax (ng/ml) OC, median: 509 vs. 335 AUC (ng•hr/ml) OC, median: 4346 vs. 2976

Oseltamivir: Studies

.Lemaitre, et al. Ther Drug Monit. 2012;34:171–5.

Eyler, et al. Pharmacotherapy. 2012;32:1061–9. Mulla, et al. Anesth Intensive Care. 2013;41:66–73.

Higher AUC of the active drug is achieved in patients receiving ECMO and therefore no dosage adjustment is necessary

Patients with renal dysfunction may experience impaired drug clearance

Oseltamivir: Key Findings

.Mulla, et al. Anesth Intensive Care. 2013;41:66–73.

Eyler, et al. Pharmacotherapy. 2012;32:1061–9.Lemaitre, et al. Ther Drug Monit. 2012;34:171–5.

Select agents previously evaluated in the literature

Consider drug properties, typically favor a high initial concentration while monitoring for potential toxicities

Monitor drug concentrations when possible

Individualize therapy, especially when targeting a specific microorganism

Antimicrobials: Considerations



Very limited data addressing the clinical outcomes associated with observational PK changes

Must rely on surrogate endpoints (WBC, temp) to assess effectiveness in the absence of therapeutic drug monitoring

Much of the existing data is l imited to simulated circuits that do not account for drug metabolism or elimination

Lack of control groups

Current studies have not fully addressed: Changing blood flow rates Different ECMO configurations Long term circuit effects Addition of renal replacement therapy

Study Limitations & Pitfalls

ECMO may be used as rescue therapy for respiratory and/or cardiorespiratory failure unresponsive to standard therapy

VA ECMO provides hemodynamic and respiratory support, whereas VV ECMO provides respiratory support alone

Significant PK alterations may occur depending on physiochemical properties of the drug & properties of the ECMO circuit

Lipophil ic drugs with high protein-binding and large volume of distribution are more susceptible to drug loss via sequestration of drug in the ECMO circuit

Hydrophil ic drugs with a small volume of distribution are greatly impacted by hemodilution

Take Home Points

Hemodilution has the greatest impact on drugs that are: (a) Lipophilic with a large Vd (b) Highly protein-bound (c) Hydrophilic with a small Vd (d) Lipophilic with low protein-binding

Learning Assessment: Question 1

Two properties that studies have shown to affect drug sequestration to the greatest degree are: (a) Lipophilicity and protein binding (b) Lipophilicity and molecular size (c) Hydrophilicity and ionization (d) Molecular size and protein binding


Current data suggest that ECMO therapy does not significantly influence voriconazole PK and thus no dosage adjustments are required. True or False?


Morphine is less lipophilic than fentanyl, making it a potentially superior option when managing patients on ECMO support. True or False?


H a M A , S i e g A C . E v a l u a t i o n o f A l t e r e d D r u g P h a r m a c o k i n e t i c s i n C r i t i c a l l y I l l A d u l t s R e c e i v i n g E x t r a c o r p o r e a l M e m b r a n e O x y g e n a t i o n . P h a r m a c o t h e r a p y . 2 0 1 7 ; 3 7 ( 2 ) : 2 2 1 – 2 3 5 .

S h e k a r K , F r a s e r J F , S m i t h M T , e t a l . P h a r m a c o k i n e t i c c h a n g e s i n p a t i e n t s r e c e i v i n g e x t r a c o r p o r e a l m e m b r a n e o x y g e n a t i o n . J C r i t C a r e . 2 0 1 2 ; 2 7 : 7 4 1 .

E L S O G u i d e l i n e s f o r C a r d i o p u l m o n a r y E x t r a c o r p o r e a l L i f e S u p p o r t . E x t r a c o r p o r e a l L i f e S u p p o r t O r g a n i z a t i o n , V e r s i o n 1 . 3 . N o v e m b e r 2 0 1 3 . A n n A r b o r , M I , U S A . w w w . e l s o n e t . o r g .

C o m b e s A , B r o d i e D , B a r t l e t t R , e t a l . P o s i t i o n P a p e r f o r t h e O r g a n i z a t i o n o f E x t r a c o r p o r e a l M e m b r a n e O x y g e n a t i o n P r o g r a m s f o r A c u t e R e s p i r a t o r y F a i l u r e i n A d u l t P a t i e n t s . A m J R e s p i r C r i t C a r e M e d . 2 0 1 4 ; 1 9 0 ( 5 ) : 4 8 8 - 9 6 .

L a f ç ı G , B u d a k A B , Y e n e r A U , e t a l . U s e o f e x t r a c o r p o r e a l m e m b r a n e o x y g e n a t i o n i n a d u l t s . H e a r t L u n g a n d C i r c . 2 0 1 4 ; 2 3 : 1 0 - 2 3 .

N i c h o l G , K a r m y - J o n e s R , S a l e r n o C , e t a l . S y s t e m a t i c r e v i e w o f p e r c u t a n e o u s c a r d i o p u l m o n a r y b y p a s s f o r c a r d i a c a r r e s t o r c a r d i o g e n i c s h o c k s t a t e s . R e s u s c i t a t i o n . 2 0 0 6 ; 7 0 ( 3 ) : 3 8 1 - 3 9 4 .

Z a p o l W M , S n i d e r M T , H i l l J D , e t a l . E x t r a c o r p o r e a l M e m b r a n e O x y g e n a t i o n i n S e v e r e A c u t e R e s p i r a t o r y F a i l u r e . A R a n d o m i z e d P r o s p e c t i v e S t u d y . J A M A . 1 9 7 9 ; 2 4 2 ( 2 0 ) : 2 1 9 3 - 2 1 9 6 .

P e e k G J , M u g f o r d M , T i r u v o i p a t i R , e t a l . ; C E S A R t r i a l c o l l a b o r a t i o n . E f f i c a c y a n d e c o n o m i c a s s e s s m e n t o f c o n v e n t i o n a l v e n t i l a t o r s u p p o r t v e r s u s e x t r a c o r p o r e a l m e m b r a n e o x y g e n a t i o n f o r s e v e r e a d u l t r e s p i r a t o r y f a i l u r e ( C E S A R ) : a m u l t i c e n t r e r a n d o m i s e d c o n t r o l l e d t r i a l . L a n c e t . 2 0 0 9 ; 3 7 4 : 1 3 5 1 - 1 3 6 3 .

G u i r a n d D M , O k o y e O T , S c h m i d t B S , e t a l . V e n o v e n o u s e x t r a c o r p o r e a l l i f e s u p p o r t i m p r o v e s s u r v i v a l i n a d u l t t r a u m a p a t i e n t s w i t h a c u t e h y p o x e m i c r e s p i r a t o r y f a i l u r e : a m u l t i c e n t e r r e t r o s p e c t i v e c o h o r t s t u d y . J T r a u m a A c u t e C a r e S u r g . 2 0 1 4 ; 7 6 ( 5 ) : 1 2 7 5 – 1 2 8 1

B o s a r g e P L , R a f f L A , M c G w i n G J r , e t a l . E a r l y i n i t i a t i o n o f e x t r a c o r p o r e a l m e m b r a n e o x y g e n a t i o n i m p r o v e s s u r v i v a l i n a d u l t t r a u m a p a t i e n t s w i t h s e v e r e a d u l t r e s p i r a t o r y d i s t r e s s s y n d r o m e . J T r a u m a A c u t e C a r e S u r g . 2 0 1 6 ; 8 1 : 2 3 6 – 2 4 3 .

B u r c h a m P K , R o z y c k i A J , A b e l E E . C o n s i d e r a t i o n s f o r a n a l g o s e d a t i o n a n d a n t i t h r o m b o t i c m a n a g e m e n t d u r i n g e x t r a c o r p o r e a l l i f e s u p p o r t . A n n T r a n s l M e d . 2 0 1 7 ; 5 ( 4 ) : 6 9 .

S h e k a r K , R o b e r t s J A , M c d o n a l d C I , e t a l . P r o t e i n - b o u n d d r u g s a r e p r o n e t o s e q u e s t r a t i o n i n t h e e x t r a c o r p o r e a l m e m b r a n e o x y g e n a t i o n c i r c u i t : r e s u l t s f r o m a n e x v i v o s t u d y . C r i t C a r e . 2 0 1 5 ; 1 9 : 1 6 4 .

D z i e r b a A L , A b r a m s D , B r o d i e D . M e d i c a t i n g p a t i e n t s d u r i n g e x t r a c o r p o r e a l m e m b r a n e o x y g e n a t i o n : t h e e v i d e n c ei s b u i l d i n g . C r i t C a r e . 2 0 1 7 ; 2 1 : 6 6 .

W a g n e r D , P a s k o D , P h i l l i p s K , e t a l . I n v i t r o c l e a r a n c e o f d e x m e d e t o m i d i n e i n e x t r a c o r p o r e a l m e m b r a n e o x y g e n a t i o n . P e r f u s i o n . 2 0 1 3 ; 2 8 : 4 0 – 6 .

S h e k a r K , R o b e r t s J A , M c D o n a l d C I , e t a l . S e q u e s t r a t i o n o f d r u g s i n t h e c i r c u i t m a y l e a d t o t h e r a p e u t i c f a i l u r e d u r i n g e x t r a c o r p o r e a l m e m b r a n e o x y g e n a t i o n . C r i t C a r e . 2 0 1 2 ; 1 6 : R 1 9 4 .

L e m a i t r e F , H a s n i N , L e p r i n c e P , e t a l . P r o p o f o l , m i d a z o l a m , v a n c o m y c i n a n d c y c l o s p o r i n e t h e r a p e u t i c d r u g m o n i t o r i n g i n e x t r a c o r p o r e a l m e m b r a n e o x y g e n a t i o n c i r c u i t s p r i m e d w i t h w h o l e h u m a n b l o o d . C r i t C a r e . 2 0 1 5 ; 1 9 : 4 0 .

S h e k a r K , R o b e r t s J A , G h a s s a b i a n S , e t a l . S e d a t i o n d u r i n g e x t r a c o r p o r e a l m e m b r a n e o x y g e n a t i o n – w h y m o r e i s l e s s . A n a e s t h I n t e n s i v e C a r e . 2 0 1 2 ; 4 0 : 1 0 6 7 – 9 .

S h e k a r K , R o b e r t s J A , M u l l a n y D V , e t a l . I n c r e a s e d s e d a t i o n r e q u i r e m e n t s i n p a t i e n t s r e c e i v i n g e x t r a c o r p o r e a l m e m b r a n e o x y g e n a t i o n f o r r e s p i r a t o r y a n d c a r d i o r e s p i r a t o r y f a i l u r e . A n a e s t h I n t e n s i v e C a r e . 2 0 1 2 ; 4 0 : 6 4 8 – 5 5 .

D e G r a d o J R , H o h l f e l d e r B , R i t c h i e B M , e t a l . E v a l u a t i o n o f s e d a t i v e s , a n a l g e s i c s , a n d n e u r o m u s c u l a r b l o c k i n g

References

F l o r o f f C K , H a s s i g T B , C o c h r a n J B , e t a l . H i g h - d o s e s e d a t i o n a n d a n a l g e s i a d u r i n g e x t r a c o r p o r e a l m e m b r a n e o x y g e n a t i o n : A f o c u s o n t h e a d j u n c t i v e u s e o f k e t a m i n e . J P a i n P a l l i a t C a r e P h a r m a c o t h e r . 2 0 1 6 ; 3 0 : 3 6 – 40 .

D z i e r b a A L , B r o d i e D , B a c c h e t t a M , e t a l . K e t a m i n e u s e i n s e d a t i o n m a n a g e m e n t i n p a t i e n t s r e c e i v i n g e x t r a c o r p o r e a l m e m b r a n e o x y g e n a t i o n . I n t e n s i v e C a r e M e d . 2 0 1 6 ; 4 2 : 1 82 2 –3 .

M e h t a N M , H a l w i c k D R , D o d s o n B L , e t a l . P o t e n t i a l d r u g s e q u e s t r a t i o n d u r i n g e x t r a c o r p o r e a l m e m b r a n e o x y g e n a t i o n : r e s u l t s f r o m a n e x v i v o e x p e r i m e n t . I n t e n s i v e C a r e M e d . 2 0 0 7 ; 3 3 : 1 01 8 –2 4 .

S h e k a r K , R o b e r t s J A , G h a s s a b i a n S , e t a l . A l t e r e d a n t i b i o t i c p h a r m a c o k i n e t i c s d u r i n g e x t r a c o r p o r e a l m e m b r a n e o x y g e n a t i o n : c a u s e f o r c o n c e r n ? J A n t i m i c r o b C h e m o t h e r 2 0 1 3 ; 6 8 : 7 26 – 72 7 .

S h e k a r K , F r a s e r J F , T a c c o n e F S , e t a l . T h e c o m b i n e d e f f e c t s o f e x t r a c o r p o r e a l m e m b r a n e o x y g e n a t i o n a n d r e n a l r e p l a c e m e n t t h e r a p y o n m e r o p e n e m p h a r m a c o k i n e t i c s : a m a t c h e d c o h o r t s t u d y . C r i t C a r e . 2 0 1 4 ; 1 8 : 5 6 5 .

D o n a d e l l o K , A n t o n u c c i E , C r i s t a l l i n i S , e t a l . B e t a - l a c t a m p h a r m a c o k i n e t i c s d u r i n g e x t r a c o r p o r e a l m e m b r a n e o x y g e n a t i o n t h e r a p y : A c a s e - c o n t r o l s t u d y . I n t J A n t i m i c r o b A g e n t s . 2 0 1 5 ; 4 5 : 2 78 – 82 .

D o n a d e l l o K , R o b e r t s J A , C r i s t a l l i n i S , e t a l . V a n c o m y c i n p o p u l a t i o n p h a r m a c o k i n e t i c s d u r i n g e x t r a c o r p o r e a l m e m b r a n e o x y g e n a t i o n t h e r a p y : a m a t c h e d c o h o r t s t u d y . C r i t C a r e . 2 0 1 4 ; 1 8 : 6 3 2 .

G é l i s s e E , N e u v i l l e M , d e M o n t m o l l i n E , e t a l . E x t r a c o p o r e a l m e m b r a n e o x y g e n a t i o n ( E C M O ) d o e s n o t i m p a c t o n a m i k a c i n p h a r m a c o k i n e t i c s :

a c a s e - c o n t r o l s t u d y . I n t e n s i v e C a r e M e d . 2 0 1 6 ; 4 2 : 9 46 – 8 . D e R o s a F G , C o r c i o n e S , B a i e t t o L , e t a l . P h a r m a c o k i n e t i c s o f l i n e z o l i d d u r i n g e x t r a c o r p o r e a l m e m b r a n e

o x y g e n a t i o n . I n t J A n t i m i c r o b A g e n t s . 2 0 1 3 ; 4 1 : 5 90 – 1 . T u r n e r R B , R o u s e S , E l b a r b r y F , e t a l . A z i t h r o m y c i n p h a r m a c o k i n e t i c s i n a d u l t s w i t h a c u t e r e s p i r a t o r y

d i s t r e s s s y n d r o m e u n d e r g o i n g t r e a t m e n t w i t h e x t r a c o r p o r e a l - m e m b r a n e o x y g e n a t i o n . A n n P h a r m a c o t h e r . 2 0 1 6 ; 5 0 : 7 2 – 3 .

V e i n s t e i n A , D e b o u v e r i e O , G r é g o i r e N , e t a l . L a c k o f e f f e c t o f e x t r a c o r p o r e a l m e m b r a n e o x y g e n a t i o n o n t i g e c y c l i n e p h a r m a c o k i n e t i c s . J A n t i m i c r o b C h e m o t h e r . 2 0 1 2 ; 6 7 : 1 0 4 7– 8 .

S p r i e t I , A n n a e r t P , M e e r s s e m a n P , e t a l . P h a r m a c o k i n e t i c s o f c a s p o f u n g i n a n d v o r i c o n a z o l e i n c r i t i c a l l y i l l p a t i e n t s d u r i n g e x t r a c o r p o r e a l m e m b r a n e o x y g e n a t i o n . J A n t i m i c r o b C h e m o t h e r . 2 0 0 9 ; 6 3 : 7 6 7– 7 0 .

R u i z S , P a p y E , D a S i l v a D , e t a l . P o t e n t i a l v o r i c o n a z o l e a n d c a s p o f u n g i n s e q u e s t r a t i o n d u r i n g e x t r a c o r p o r e a l m e m b r a n e o x y g e n a t i o n . I n t e n s i v e C a r e M e d 2 0 0 9 ; 3 5 ( 1 ) : 1 8 3– 4 .

L e m a i t r e F , L u y t C E , R o u l l e t - R e n o l e a u F , e t a l . I m p a c t o f e x t r a c o r p o r e a l m e m b r a n e o x y g e n a t i o n a n d c o n t i n uo u s v e n o v e n o us h e m o d i a f i l t r a t i o n o n t h e p h a r m a c o k i n e t i c s o f o s e l t a m i v i r c a r b o x y l a t e i n c r i t i c a l l y i l l p a t i e n t s w i t h p a n de m i c ( H 1 N 1 ) i n f l u e n z a . T h e r D r u g M o n i t . 2 0 1 2 ; 3 4 : 1 71 – 5 .

E y l e r R F , H e u n g M , P l e v a M , e t a l . P h a r m a c o k i n e t i c s o f o s e l t a m i v i r a n d o s e l t a m i v i r c a r b o x y l a t e i n c r i t i c a l l y i l l p a t i e n t s r e c e i v i n g c o n t i n u ou s v e n o v e no u s h e m o d i a l y s i s a n d / o r e x t r a c o r p o r e a l m e m b r a n e o x y g e n a t i o n . P h a r m a c o t h e r a py . 2 0 1 2 ; 3 2 : 1 06 1 –9 .

M u l l a H , P e e k G J , H a r v e y C , e t a l . O s e l t a m i v i r p h a r m a c o k i n e t i c s i n c r i t i c a l l y i l l a d u l t s r e c e i v i n g e x t r a c o r p o r e a l m e m b r a n e o x y g e n a t i o n s u p p o r t . A n e s t h I n t e n s i v e C a r e . 2 0 1 3 ; 4 1 : 6 6 – 73 .

References

Documents

Drug Selection & Dosing in Patients on Extracorporeal ... · PDF filePatients on Extracorporeal Membrane Oxygenation ... Cardiogenic shock ... et al.Pharmacotherapy. 2016;36:607–16