TITLE: Short-Acting Spinal Anesthetics for Outpatient ... · Short-acting Spinal Anesthetics for Outpatient Procedures 4 Outcomes measured All studies reported on side effects or

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TITLE: Short-Acting Spinal Anesthetics for Outpatient Procedures: A Review of the Clinical Evidence and Guidelines

DATE: 4 May 2011 CONTEXT AND POLICY ISSUES: A trend towards outpatient surgical procedures requires a drug that provides adequate anesthesia with rapid recovery and minimal side effects. Many of these procedures are performed with spinal anesthesia, which involves delivery of local anesthetic via lumbar puncture into the subarachnoid space. In the past, lidocaine has been a popular choice as a spinal anesthetic due to rapid regression of sensory and motor block.1 However, its use has declined due to concerns about adverse events.2,3 One of these side effects, transient neurologic symptoms (TNS), manifests as light to severe pain originating in the buttocks and radiating to the lower extremities, which may be a sign of neurotoxicity.2,4 Related drugs, such as bupivacaine, have lower incidence of TNS but require longer recovery times and may not be ideal for use in outpatient surgery.4,5 Other local anesthetics used for spinal anesthesia in an ambulatory setting include chloroprocaine, articaine, ropivacaine, and prilocaine.2 These drugs, including bupivacaine and lidocaine, are available for use in Canada. The purpose of this review is to examine the clinical evidence and guidelines regarding optimal administration and safety of short-acting spinal anesthetics. RESEARCH QUESTIONS:

1. What is the clinical evidence regarding the optimal short-acting spinal anesthetic administration for outpatient procedures?

2. What is the clinical evidence regarding the safety of spinal administration of short-acting anesthetic agents?

3. What are the evidence-based guidelines regarding the use of short-acting spinal anesthetic administration for outpatient procedures?

Short-acting Spinal Anesthetics for Outpatient Procedures 2

KEY MESSAGE: Spinal administration of local anesthetics provides adequate anesthesia with low rates of adverse events, but further research is needed to determine optimal use and safety. METHODS: Literature search strategy

A limited literature search was conducted on key resources including Ovid MEDLINE, PubMed, The Cochrane Library (2011, Issue 3), University of York Centre for Reviews and Dissemination (CRD) databases, Canadian and major international health technology agencies, as well as a focused Internet search. No methodological filters were applied to limit retrieval by study type. Where possible, retrieval was limited to the human population. The search was also limited to English language documents published between January 1, 2006 and April 5, 2011. Selection criteria and method One reviewer (CK) screened the titles and abstracts of the retrieved publications and evaluated the full-text publications for the final article selection, according to selection criteria presented in Table 1. Table 1: Selection Criteria

Population

Adult patients undergoing outpatient or short term procedures requiring anesthetic

Intervention Spinally administered short-acting anesthetics

Comparator Not specified

Outcomes Anesthetic effect, safety, guidelines, and best practices

Study designs

Health technology assessments, systematic reviews, meta-analyses, randomized controlled trials (RCTs),observational studies, and evidence-based guidelines.

Exclusion criteria Studies were excluded if they did not meet the selection criteria, were duplicate publications or included in a selected systematic review, involved drugs not available in Canada, or were published prior to 2006. Critical appraisal of individual studies The quality of included systematic reviews was assessed using the Assessment of Multiple Systematic Reviews (AMSTAR) tool.6 RCT and non-randomized study quality were evaluated using the Downs and Black instrument.7 A numeric score was not calculated for each study. Instead, strengths and weakness of each study were summarized and described.


SUMMARY OF EVIDENCE: Quantity of research available The literature search yielded 254 citations. Upon screening titles and abstracts, 233 citations were excluded and 21 potentially relevant articles were retrieved for full-text review. An additional three potentially relevant reports were identified through grey literature searching. Of the 24 potentially relevant reports, seven did not meet the inclusion criteria. Seventeen publications were included in this review. The study selection process is outlined in a PRISMA flowchart (Appendix 1). Two systematic reviews, 14 RCTs, and one retrospective cohort study met inclusion criteria. No evidence-based clinical practice guidelines were identified. Summary of study characteristics Details on study characteristics, critical appraisal and findings can be found in Appendices 2, 3 and 4, respectively. Country of origin Both systematic reviews, one from a group in Canada5 and one from the USA,2 included RCTs from multiple different countries. Three included studies8-10 came from Brazil, two each came from Finland,11,12 Italy,13,14 and the Netherlands,15,16 and Canada,17 Egypt,18 Estonia,19 Switzerland,20 Turkey,21 and the USA22 were the source of one study each. Study setting In one systematic review5 and four RCTs9,18-20 performed procedures in an ambulatory setting. Four RCTs11,12,15,16 involved day-case procedures. Six RCTs8,10,13,14,17,21 and one cohort study22 described their cases as outpatient procedures. One systematic review2 was not limited to a particular surgical setting and included ambulatory and non-ambulatory procedures. Patient population All studies included adult patients undergoing outpatient or ambulatory procedures with spinal anaesthesia, with an overall age range of 18 to 83 years old. Two studies included patients undergoing anorectal surgery.8,10 Six studies, including one systematic review, included patients undergoing knee arthroscopy.5,11,13,15,18,21 In four studies, lower limb procedures were performed, which include arthroscopy but also other surgeries (for example, saphenectomy).12,14,16,19 The remaining five studies, including one systematic review, did not restrict inclusion to a single procedure type and each included patients undergoing various surgeries.2,9,17,20,22 Interventions and comparators Seven studies compared different doses of spinal anesthetics.5,10,12,14,18-20 Two of these examined bupivacaine dose,5,18 two examined chloroprocaine dose,14,19 and one each looked at different doses of lidocaine,10 or articaine.12 Ten studies compared different spinal anesthetics,2,5,8,11,13,15-17,21,22 but only one pairwise comparison (bupivacaine versus ropivacaine) was identified more than once.5,21 One study9 compared the same dose but different concentrations of lidocaine. One study20 compared hyperbaric to plain (isobaric) prilocaine.


Outcomes measured All studies reported on side effects or adverse events. One systematic review2 focused exclusively on transient neurologic symptoms following spinal anesthesia with lidocaine versus other anesthetics. Twelve studies reported peak block height, assessed by loss of pinprick sensation at a particular dermatome (an area of the skin supplied by a single spinal nerve)8-

17,19,21 and seven11-13,15,17,20,21 reported the time to onset of this maximum block. Time to resolution of sensory8-14,17,19,20 or motor15,16,18,21,22 block was reported in fifteen studies. Resolution of sensory block was assessed by return of sensation to a pre-determined dermatome level, as assessed by pin prick. Motor block was assessed by a modified Bromage scale, which assesses the patient’s ability to move the lower limbs. Eleven studies reported time to hospital discharge.5,11-14,16,17,19-22 Summary of critical appraisal The quality of evidence identified was generally high. With the exception of one cohort study22, all reports were RCTs or systematic reviews of RCTs. Two systematic reviews2,5 were based on comprehensive literature search, but it was unclear whether grey literature was included in the search strategy. The possibility of publication bias was investigated by one review.2 Fourteen RCTs were included in the review. Of these, 12 described an adequate method of randomization,8-14,17-21 while the other two did not describe the randomization method.15,16 Both patients and outcome assessors were blinded in each trial, with the exception of one single-blind trial21 where outcome assessors were aware of the intervention. Ten studies performed a power calculation to determine an adequate sample size for detecting clinically significant differences.8,11-17,19,20 One retrospective cohort study was identified.22 This study included a large number of patients, reflecting the current practice at an American medical centre. Because it reflects current practice, there was a large discrepancy in the number of patients receiving each intervention. Additionally, doses of different anesthetics were not equipotent so direct comparisons of discharge times may not be appropriate. Summary of findings Comparison of anesthetics One systematic review5 and four RCTs8,16,17,21 compared the use of bupivacaine with other spinal anaesthetics. Bupivacaine had a longer time to block resolution compared with articaine, chloroprocaine, lidocaine, and ropivacaine, though this did not translate into shorter discharge times in the case of ropivacaine. One case of transient neurologic symptoms was reported with articaine. One study17 reported one case of TNS each for bupivacaine and chloroprocaine, and higher rates of post-anesthesia pain with chloroprocaine. One study15 compared articaine with prilocaine and found a faster resolution of motor block with articaine but no difference in time to discharge. A single case of TNS was reported in this study, in the articaine group. A different study11 comparing articaine to chloroprocaine found that patients receiving chloroprocaine were found to have faster recovery from sensory block and shorter times to discharge with no cases of TNS reported, however discharge times were not based on defined criteria. One cohort study22 showed that chloroprocaine had a better recovery


profile and resulted in shorter time to discharge compared with lidocaine. Lidocaine use was shown in one study13 to result in shorter time to sensory block recovery and discharge compared to ropivacaine but at the cost of higher rates of TNS and injection site pain. Anesthetic dose One systematic review5 and one RCT18 compared different doses of bupivacaine. Doses, as low as 4 to 5 mg, were shown to produce enough anesthesia with low failure rate in the unilateral position. Higher doses resulted in longer recovery times without any significant changes in adverse events. Two RCTs14,19 examined different doses of chloroprocaine. Both found doses of 40 mg resulted in faster resolution of spinal block. One study19 showed that higher doses resulted in longer time to discharge, while the other14 reported that reduced doses resulted in insufficient duration of anesthesia with no advantage in terms of time to discharge. One study12 reported that different doses of articaine did not significantly affect the block profile or discharge times for patients, but at the highest dose used (108 mg) there was significantly more nausea and vomiting, and a greater need for rescue medication for hypotension. Similarly with lidocaine, a larger, but not statistically significant, number of patients experienced bradycardia at higher doses, while the lowest dose used (18 mg) provided sufficient analgesia with shorter duration. Concentration and baricity The effect of the same dose but different concentration of spinal anesthetic was examined in one study, which showed no difference in block height or duration with two different concentrations of lidocaine.9 Baricity, or solution density compared to spinal fluid, was examined in one study that showed shorter time to peak sensory block and resolution of sensory block with hyperbaric compared to plain (isobaric) prilocaine.20 Low rates of TNS were reported across all included studies, with the exception of one RCT13 that reported TNS in 40% of patients receiving lidocaine versus zero among those treated with ropivacaine. One systematic review examined TNS rates following anesthesia with lidocaine compared to other anesthetics and found the risk of developing TNS was significantly higher than with other local anesthetics.2 This review was not limited to ambulatory procedures. Limitations One systematic review2 focusing on safety included non-ambulatory surgeries and may not reflect issues specific to anesthesia for outpatient or short-term procedures. All other included reports included only ambulatory, outpatient, or day-case procedures, but surgery type varied across studies which may affect generalizability. Generalizability is further impaired by the small number of studies available for each comparison. Though the studies were generally well conducted, single studies may not be adequate to draw conclusions about optimal spinal anesthetic administration.


While most included RCTs performed a power calculation to determine an appropriate sample size, these calculations were based on time to block resolution or discharge, and the trials may not be sufficiently large to detect differences in safety outcomes. Because rapid response reports involve a more limited literature search than a full systematic review, the drugs identified in evidence may not be exhaustive of all local anesthetics available for spinal delivery in Canada. The use of adjuvants in combination with spinal delivery of local anesthetics was deemed outside the scope of this review. CONCLUSIONS AND IMPLICATIONS FOR DECISION OR POLICY MAKING: All the spinal anesthetics examined in the selection studies provided adequate block for outpatient and short-term procedures. Bupivacaine use tended to result in longer time for block resolution compared with other spinal anesthetics while chloroprocaine was associated with shorter recovery and discharge times. This outcome, however, is based on limited evidence and further research is required to determine optimal spinal anesthetic administration. The use of lidocaine was associated with higher rates of TNS following spinal anesthesia. The rates of TNS and other adverse events were low among other anesthetics across the included trials. The findings suggest that spinal administration of these drugs is safe, but the included trials may have been underpowered to detect rare adverse events. Larger studies are required to draw definite conclusions regarding safety profiles. Conclusions on the best practices regarding the use of short-acting spinal anesthetic administration for outpatient procedures cannot be drawn since no relevant evidence-based guidelines were identified. PREPARED BY: Canadian Agency for Drugs and Technologies in Health Tel: 1-866-898-8439 www.cadth.ca

http://www.cadth.ca/


REFERENCES: 1. Liu SS. Drugs for spinal anesthesia: past, present, and future. Reg Anesth Pain Med. 1998

Jul;23(4):344-6.

2. Zaric D, Pace NL. Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics. Cochrane Database Syst Revs [Internet]. 2009 [cited 2011 Apr 5];(2):CD003006. Available from: http://www.thecochranelibrary.com/view/0/index.html Subscription required.

3. Freedman JM, Li DK, Drasner K, Jaskela MC, Larsen B, Wi S. Transient neurologic symptoms after spinal anesthesia: an epidemiologic study of 1,863 patients. Anesthesiology. 1998 Sep;89(3):633-41.

4. Hampl KF, Heinzmann-Wiedmer S, Luginbuehl I, Harms C, Seeberger M, Schneider MC. Transient neurologic symptoms after spinal anesthesia: a lower incidence with prilocaine and bupivacaine than with lidocaine. Anesthesiology. 1998 Sep;88(3):629-33.

5. Nair GS, Abrishami A, Lermitte J, Chung F. Systematic review of spinal anaesthesia using bupivacaine for ambulatory knee arthroscopy. Br J Anaesth [Internet]. 2009 Mar [cited 2011 Apr 11];102(3):307-15. Available from: http://bja.oxfordjournals.org/content/102/3/307.full.pdf+html

6. Shea BJ, Grimshaw JM, Wells GA, Boers M, Andersson N, Hamel C, et al. Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews. BMC Med Res Methodol [Internet]. 2007 [cited 2011 Apr 19];7:10. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1810543/pdf/1471-2288-7-10.pdf

7. Downs SH, Black N. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. J Epidemiol Community Health [Internet]. 1998 Jun [cited 2010 Sep 15];52(6):377-84. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1756728/pdf/v052p00377.pdf

8. Imbelloni LE, Gouveia MA, Cordeiro JA. Hypobaric 0.15% bupivacaine versus hypobaric 0.6% lidocaine for posterior spinal anesthesia in outpatient anorectal surgery. Revista Brasileira de Anestesiologia [Internet]. 2010 Apr [cited 2011 Apr 11];60(2):113-20. Available from: http://www.scielo.br/pdf/rba/v60n2/en_v60n2a02.pdf

9. Imbelloni LE, Gouveia MA, Cordeiro JA. Low dose of lidocaine: comparison of 15 with 20 mg/ml with dextrose for spinal anesthesia in lithotomy position and ambulatory surgery. Acta Anaesthesiol Scand. 2008 Jul;52(6):856-61.

10. Imbelloni LE, Gouveia MA, Vieira EM, Cordeiro JA. Selective sensory spinal anaesthesia with hypobaric lidocaine for anorectal surgery. Acta Anaesthesiol Scand. 2008 Nov;52(10):1327-30.

11. Forster JG, Kallio H, Rosenberg PH, Harilainen A, Sandelin J, Pitkanen MT. Chloroprocaine vs. articaine as spinal anaesthetics for day-case knee arthroscopy. Acta Anaesthesiol Scand. 2011 Mar;55(3):273-81.

http://www.thecochranelibrary.com/view/0/index.html

http://bja.oxfordjournals.org/content/102/3/307.full.pdf+html

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1810543/pdf/1471-2288-7-10.pdf

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1756728/pdf/v052p00377.pdf

http://www.scielo.br/pdf/rba/v60n2/en_v60n2a02.pdf


12. Kallio H, Snall EV, Luode T, Rosenberg PH. Hyperbaric articaine for day-case spinal anaesthesia. Br J Anaesth. 2006 Nov;97(5):704-9.

13. Fanelli G, Danelli G, Zasa M, Baciarello M, Di Cianni S., Leone S. Intrathecal ropivacaine 5 mg/ml for outpatient knee arthroscopy: a comparison with lidocaine 10 mg/ml. Acta Anaesthesiol Scand. 2009 Jan;53(1):109-15.

14. Casati A, Danelli G, Berti M, Fioro A, Fanelli A, Benassi C, et al. Intrathecal 2-chloroprocaine for lower limb outpatient surgery: a prospective, randomized, double-blind, clinical evaluation. Anesthesia & Analgesia. 2006 Jul;103(1):234-8.

15. Hendriks MP, de Weert CJ, Snoeck MM, Hu HP, Pluim MA, Gielen MJ. Plain articaine or prilocaine for spinal anaesthesia in day-case knee arthroscopy: a double-blind randomized trial. Br J Anaesth [Internet]. 2009 Feb [cited 2011 Apr 11];102(2):259-63. Available from: http://bja.oxfordjournals.org/content/102/2/259.full.pdf+html

16. Dijkstra T, Reesink JA, Verdouw BC, Van der Pol WS, Feberwee T, Vulto AG. Spinal anaesthesia with articaine 5% vs bupivacaine 0.5% for day-case lower limb surgery: a double-blind randomized clinical trial. Br J Anaesth [Internet]. 2008 Jan [cited 2011 Apr 11];100(1):104-8. Available from: http://bja.oxfordjournals.org/content/100/1/104.full.pdf+html

17. Lacasse MA, Roy JD, Forget J, Vandenbroucke F, Seal RF, Beaulieu D, et al. Comparison of bupivacaine and 2-chloroprocaine for spinal anesthesia for outpatient surgery: a double-blind randomized trial. Can J Anaesth. 2011 Apr;58(4):384-91.

18. Atef HM, El-Kasaby AM, Omera MA, Badr MD. Optimal dose of hyperbaric bupivacaine 0.5% for unilateral spinal anesthesia during diagnostic knee arthroscopy. Local and Regional Anesthesia [Internet]. 2010 [cited 2011 Apr 5];3:85-91. Available from: http://www.dovepress.com/getfile.php?fileID=7494

19. Sell A, Tein T, Pitkanen M. Spinal 2-chloroprocaine: effective dose for ambulatory surgery. Acta Anaesthesiol Scand. 2008 May;52(5):695-9.

20. Camponovo C, Fanelli A, Ghisi D, Cristina D, Fanelli G. A prospective, double-blinded, randomized, clinical trial comparing the efficacy of 40 mg and 60 mg hyperbaric 2% prilocaine versus 60 mg plain 2% prilocaine for intrathecal anesthesia in ambulatory surgery. Anesthesia & Analgesia. 2010 Aug;111(2):568-72.

21. Boztug N, Bigat Z, Karsli B, Saykal N, Ertok E. Comparison of ropivacaine and bupivacaine for intrathecal anesthesia during outpatient arthroscopic surgery. J Clin Anesth. 2006 Nov;18(7):521-5.

22. Hejtmanek MR, Pollock JE. Chloroprocaine for spinal anesthesia: a retrospective analysis. Acta Anaesthesiol Scand. 2011 Mar;55(3):267-72.



http://www.dovepress.com/getfile.php?fileID=7494


APPENDICES: APPENDIX 1: Selection of Included Studies

233 citations excluded

21 potentially relevant articles retrieved for scrutiny (full text, if

available)

3 potentially relevant reports retrieved from other sources (grey

literature, hand search)

24 potentially relevant reports

7 reports excluded: -irrelevant intervention (1) -irrelevant outcomes (4) -already included in at least one of the selected systematic reviews (2)

17 reports included in review

254 citations identified from electronic literature search and

screened


APPENDIX 2: Summary of Study Characteristics

First Author, Publication Year, Country

Study Design

Patient Characteristics

Intervention Comparator Clinical Outcomes Measured

Nair5

2009 Canada

Systematic Review

17 RCTs including 1,268 patients undergoing knee arthroscopy

Spinal anesthesia using bupivacaine

Ropivacaine (5 trials), bupivacaine dose (5 trials)

Sensory block, time to discharge, adverse events

Zaric2

2009 USA

Systematic Review

16 RCTs including 1,479 patients undergoing various procedures

Spinal anesthesia with lidocaine

Bupivacaine (7 trials) Prilocaine (4 trials) Ropivacaine (1 trial) Chloroprocaine (1 trial)

Transient neurologic symptoms

Förster11

2011 Finland

Double-blind RCT (closed envelope, block)

80 adult patients scheduled for ambulatory knee arthroscopy

20 mg/mL plain chloroprocaine 40 mg (n = 40)

40 mg/mL plain articaine 60 mg (n = 40)

Motor and sensory block, recovery from block, sequelae

Lacasse17

2011 Canada

Double-blind RCT (computer generated)

106 adult patients scheduled for elective ambulatory surgery (< 1 hour)

0.75% hyperbaric bupivacaine 7.5 mg (n = 53)

2% 2-chloroprocaine 40 mg (n = 53)

Time to discharge, sensory block, adverse events

Atef18

2010 Egypt

Double-blind RCT (sealed envelope)

80 adult patients undergoing diagnostic knee arthroscopy

0.5% hyperbaric bupivacaine, 5 mg (n = 20)

0.5% hyperbaric bupivacaine 7.5 mg (n = 20), 10 mg (n = 20), 12.5 mg (n = 20)

Motor and sensory block, regression time, complications

Camponovo20

2010 Switzerland

Double-blind RCT (random number generator)

90 adult patients scheduled for any short surgical procedure (< 1 hour)

2% plain prilocaine 60 mg (n = 30)

2% hyperbaric prilocaine 40 mg (n = 30) 2% hyperbaric prilocaine 60 mg (n = 30)

Motor and sensory block, time to discharge, side effects

Imbelloni8

2010 Brazil


150 adult patients scheduled for outpatient anorectal surgery

0.15% hypobaric bupivacaine 4.5 mg (n = 75)

0.6% hypobaric lidocaine 18 mg (n = 75)

Sensory and motor blockade, time for patient recovery, side effects

Fanelli13

2009

Double-blind RCT

30 adult patients undergoing knee

10 mg/mL plain lidocaine

5 mg/mL plain ropivacaine

Motor and sensory block,



Study Design



Italy (computer generated)

arthroscopy 50 mg (n = 15)

10 mg (n = 15)

time to discharge, transient neurologic symptoms

Hendriks15

2009 The Netherlands

Double-blind RCT

72 adult patients undergoing day-case knee arthroscopy

50 mg plain prilocaine (n = 36)

50 mg plain articaine (n = 36)

Motor and sensory block, side effects

Dijkstra16

2008 The Netherlands

Double-blind RCT (block randomization)

80 adult patients scheduled for day-case lower limb surgery

plain bupivacaine 15 mg (n = 40)

Hyperbaric articaine 80 mg (n = 40)

Recovery time from motor block, discharge time, complications

Imbelloni9

2008 Brazil


100 adult patients undergoing short (1 hour) surgical procedures

15 mg/mL hyperbaric lidocaine 30 mg (n = 50)

20 mg/mL hyperbaric lidocaine 30 mg (n = 50)

Motor and sensory block, transient neurologic symptoms

Imbelloni10

2008 Brazil


150 adult patients scheduled for outpatient anorectal surgery

0.6% hypobaric lidocaine 18 mg (n = 50)

0.6% hypobaric lidocaine 24 mg (n = 50), 30 mg (n = 50)

Sensory and motor blockade, complications

Sell19

2008 Estonia


64 adult patients scheduled for lower limb surgery under ambulatory settings

10 mg/mL isobaric 2-chloroprocaine 35 mg (n = 16)

10 mg/mL isobaric 2-chloroprocaine 40 mg (n = 16) 45 mg (n = 16) 50 mg (n = 16)

Motor and sensory block, recovery profile

Boztuğ21

2006 Turkey

Single-blind RCT (random number generator)

90 adult patients scheduled for knee arthroscopies

isobaric bupivacaine 7.5 mg (n = 45)

isobaric ropivacaine 15 mg (n = 45)

Motor and sensory block, time to discharge, complications

Casati14

2006 Italy


45 adult patients undergoing elective outpatient lower limb surgery

1% 2-chloroprocaine 30 mg (n = 15)

1% 2-chloroprocaine 40 mg (n = 15) 50 mg (n = 15)

Motor and sensory block, resolution of block

Kallio12

2006 Finland

Double-blind RCT (random number generator/block allocation)

90 adult day-case lower extremity surgical patients

Articaine 60 mg (n = 30)

Articaine 84 mg (n = 30) 108 (n = 30)

Sensory and motor block, time for patient recovery, side effects

Hejtmanek22

2011 USA

Retrospective cohort

563 patients undergoing 601 ambulatory

Any spinal anesthesia

Chloroprocaine median dose 40 mg, n = 503

Block characteristics side effects



Study Design



procedures with spinal anesthesia

Lidocaine median dose 60 mg, n = 84 Other, n = 14


APPENDIX 3: Summary of Critical Appraisal

First Author, Publication Year

Strengths Limitations

Systematic Reviews Nair

5

2009 Comprehensive literature search based on pre-defined criteria.

Lack of description of study characteristics and excluded studies.

Unclear whether grey literature was searched.

Zaric2

2009 Comprehensive literature search based on pre-defined criteria.

Summary of study characteristics and list of included and excluded studies was provided.

Risk of publication bias investigated with a funnel plot.

Unclear whether grey literature was included.

Studies included a variety of surgeries, including non-ambulatory procedures.

Randomized Controlled Trials Förster

11

2011 Patients and outcome assessors blinded.

Adequate method of randomization. Power calculation performed to determine adequate sample size.

Losses to follow-up described

Anesthesiologist not blinded.

Protocol focused on spinal block recovery, not discharge time which was not standardized.

Lacasse17

2011

Adequate randomization method.

Patients and data collectors blinded.

Power calculation performed based on pilot study.

All patients received assigned treatment.


Atef18

2010


Outcome assessors blinded.

No power calculation to determine adequate sample size.

No description of conversions to general anesthetic.

Camponovo20

2010


Patients and outcome assessors blinded.

Adverse events and losses to follow-up described.

Power calculation was performed.

Study designed as a non-inferiority trial.

Imbelloni8

2010 Patients and outcome assessors blinded.

Adequate method of randomization.

Power calculation performed to determine sample size.

Power calculation based on duration of motor blockade and may not be adequate to detect differences in secondary outcomes.

Fanelli13

2009



Power calculation performed to determine adequate sample size.


Power calculation based on data related to sensory block regression and small sample size may not be adequate for secondary outcomes.

Hendriks15

2009


Power calculation performed to determine adequate sample size.

Adverse events described.

Method of randomization not described.

Dijkstra16

Patients and outcome assessors blinded. Patients were randomized in blocks, but



Strengths Limitations

2008 Power calculation was performed to determine appropriate sample size.

Description of losses to follow-up.

method of randomization was not described.

Study population was not large enough to detect rare side-effects.

Patients lost to follow-up not accounted for in the analysis.

Imbelloni9

2008 Adequate randomization method.

Patients, surgeons, and assessors were blinded.

All patients received assigned treatment (no conversions to general anesthetic)

No power calculation was performed, but authors claim sample size reliable for TNS detection

Imbelloni10

2008



No power calculation performed to determine sample size required to detect clinically relevant outcomes.

Sell19

2008


Adequate randomization.

Power calculation was performed to determine sample size.

Sample size inadequate to conclude the safety profile of spinal administration of the drug.

Boztuğ21

2006


Patients blinded.

Outcome assessors not blinded.

No power calculation to determine adequate sample size.

No description of conversions to general anesthetic or losses to follow-up.

Casati14

2006


Adequate randomization.

Power calculation was performed to determine sample size.

Sample size inadequate to conclude the safety profile of spinal administration of the drug.

Kallio12

2006



Power calculation performed to determine sample size.

Power calculation was based on sensory block recovery and may not be adequate for identifying clinically relevant differences in adverse event rates.

Cohort Study Hejtmanek

22

2011 Large cohort of patients, reflects current practice

No randomization or blinding.

Discrepancy between numbers of patients receiving each anesthetic.


APPENDIX 4: Summary of Findings


Main Study Findings Authors’ Conclusions

Systematic reviews Nair

5

2009 Five trials compared different bupivacaine doses (5 mg to 15 mg). Data were not pooled. Low doses (4 to 5 mg) resulted in similar block height but shorter recovery times compared to higher doses (P < 0.05). Mean discharge time ranged from 180 to 240 minutes across all studies. No TNS were reported and complication rate (e.g. headache or nausea) ranged from 0% to 4% but was not significantly different between the studies. Five trials compared ropivacaine to bupivacaine. Data were not pooled. Two trials showed longer time to onset and shorter time to recovery from sensory block with ropivacaine, but there was no difference in time to discharge or side effects compared with bupivacaine.

“Our results suggest that low doses of hyperbaric bupivacaine 4-5 mg can effectively produce spinal anaesthesia with unilateral positioning in knee arthroscopy. Higher doses or bilateral positioning may result in delayed recovery or high rate of failure, respectively. Ropivacaine or the addition of adjuvants did not improve recovery time.” p. 312

Zaric2

2009 Compared with other spinal anesthetics, including bupivacaine, prilocaine, procaine, ropivacaine, mepivacaine and chloroprocaine, the pooled data indicated that the relative risk of developing TNS is higher with lidocaine (RR 4.62 95% CI 2.30 to 9.26, P < 0.0001). When mepivacaine is removed from the analysis, the relative risk increases (RR 7.31, 95% CI 4.16 to 12.86, P < 0.00001).

“The relative risk of developing TNS is about seven times higher for lidocaine than for bupivacaine, prilocaine, procaine, ropivacaine and levobupivacaine. [...] The risk of TNS weighted against the benefit of rapid, short-acting anaesthesia and the patient’s viewpoint must be considered in the decision as to whether to use lidocaine for ambulatory anaesthesia. Bupivacaine, prilocaine, and procaine are associated with lower risks of TNS but longer duration or lower quality of anesthesia may limit their suitability for ambulatory surgery.” p. 10-11

Randomized controlled trials Förster

11

2011 Median peak block height, time to onset: Chloroprocaine: T10, 20 min Articaine: T10, 20 min Time to full sensory block recovery Chloroprocaine: 105 min Articaine: 165 min P < 0.0001 (95% CI not reported) Mean time to discharge Chloroprocaine: 318 ± 74.2 min Articaine: 392 ± 93.2 min

“Both anaesthetics used provided a rapid onset of spinal anaesthesia for about 1 h and were satisfactory for day-case knee arthroscopy. Recovery, however, was significantly faster in group C40. [40 mg chloroprocaine]” p. 273




P = 0.004 No difference between groups regarding sequelae. No cases of TNS were reported.

Lacasse17

2011

Mean peak block height, time to onset: Chloroprocaine: T7, 15 ± 8 min Bupivacaine: T7, 18 ± 11 min Mean difference: 2.8 min 95% CI -1.1 to 6.7 Time to full sensory block recovery: Chloroprocaine: 146 ± 38 min Bupivacaine: 329 ± 82 min P < 0.001 Mean difference: 185.4 min 95% CI 158.5 to 212.4 Mean time to discharge: Chloroprocaine: 277 ± 87 min Bupivacaine: 353 ± 99 min P < 0.001 Mean difference: 75.9 min 95% CI 39.9 to 112.0 Chloroprocaine patients experienced more post-anesthesia pain (19% difference, P = 0.007) No difference in complication rate. One TNS case reported in each group.

“Spinal 2-chloroprocaine provides adequate duration and depth of surgical anesthesia for short procedures with the advantages of faster block resolution and earlier hospital discharge compared with spinal bupivacaine.” p. 384

Atef18

2010

Unilateral sensory block: Bupivacaine 5 mg: 90% of patients Bupivacaine 7.5 mg: 85% Bupivacaine 10 mg, 12.5 mg: 0% Time to regression of motor block: Bupivacaine 5 mg: 59.8 ± 14.6 min Bupivacaine 7.5 mg: 98.3 ± 15.8 min Bupivacaine 10 mg: 123.6 ± 9.7 min Bupivacaine 12.5 mg: 148.9 ± 10.3 min Incidence of nausea, vomiting, and urine retention was similar between groups. Three patients receiving 5 mg and one receiving 7.5 mg required rescue analgesia (P = 0.09, 95% CI not reported)

”Unilateral sensory and motor block can be achieved with doses of 5 mg and 7.5 mg hyperbaric bupivacaine 0.5% with a stable hemodynamic state. However, 7.5 mg of hyperbaric bupivacaine 0.5% was the dose required for adequate unilateral spinal anesthesia.” p. 85

Camponovo20

2010

Time to T10 sensory block was comparable between the groups, but 20% of patients receiving plain prilocaine did not reach T10. Time to peak sensory block (min): Hyperbaric prilocaine 60 mg: 18 ± 13

Spinal anesthesia with 60 mg or 40 mg of 2% hyperbaric prilocaine is comparable to 60 mg of 2% plain prilocaine in terms of onset of sensory block at T10. The hyperbaric solution showed faster times to motor block




Hyperbaric prilocaine 40 mg: 15 ± 7 Plain prilocaine 60 mg: 25 ± 18 60 mg hyperbaric versus 60 mg plain, P = 0.0297 40 mg hyperbaric versus 60 mg plain, P = 0.0183 (95% CI not reported) Time to resolution of sensory block (min): Hyperbaric prilocaine 60mg: 118 ± 37 Hyperbaric prilocaine 40 mg: 92 ± 36

d

Plain prilocaine 60 mg: 157 ± 41cd

60 mg hyperbaric versus 60 mg plain, P = 0.0004 40 mg hyperbaric versus 60 mg plain, P < 0.0001 Time to discharge (min): Hyperbaric prilocaine 60 mg: 256 ± 85 Hyperbaric prilocaine 40 mg: 208 ± 68 Plain prilocaine 60 mg: 299 ± 101 40 mg hyperbaric versus 60 mg plain, P = 0.0004 No major adverse reactions or TNS reported

onset and shorter duration of surgical block, suggesting its superiority for the ambulatory setting.” p. 568

Imbelloni8

2010

Median peak block height at 60 min: Bupivacaine: L3 (IQR L1 to T12) Lidocaine : L5 (IQR L1 to T12) P < 0.0005 Mean blockade duration (min): Bupivacaine: 99.1 ± 11.0 Lidocaine: 64.1 ± 7.6 P < 0.0005 (95% CI not reported) No adverse events or TNS reported

”Hypobaric lidocaine provides analgesia with the same dispersion of that of bupivacaine, but with shorter duration.” p. 113

Fanelli13

2009

Median peak block height, time to onset: Lidocaine: T10, 15 min Ropivacaine: T10, 24 min P = NS (95% CI not reported) Median time to full sensory block recovery (IQR): Lidocaine: 148 min (130 to 167) Ropivacaine: 188 min (146 to 231) P = 0.022 Median time to discharge (IQR) Lidocaine: 210 min (170 to 250) Ropivacaine: 293 min (245 to 350) P = 0.001

”Spinal block produced with 10 mg ropivacaine 5 mg/mL is as effective as that produced by 50 mg of lidocaine 10 mg/ml. Recovery of unassisted ambulation and spontaneous voiding occurred earlier with lidocaine, but this was associated with markedly higher incidence of TNS.” p. 109




At 24 hour follow-up, four patients (27%) receiving lidocaine reported pain at the injection site compared to zero receiving ropivacaine (P = 0.042) Six patients (40%) receiving lidocaine versus zero receiving ropivacaine reported TNS (P = 0.005). In all cases, TNS resolved spontaneously within a week.

Hendriks15

2009

Median peak block height, time to onset: Articaine: T10, 10 min Prilocaine: T10, 10 min Mean time to full motor block recovery: Articaine: 140 ± 33 minutes Prilocaine: 184 ± 45 minutes P < 0.001 (95% CI not reported) One patient receiving articaine and none receiving prilocaine reported TNS. There were no significant differences in adverse events between groups.

“Spinal anesthesia with plain articaine 50 mg resulted in a faster recovery of motor function and earlier spontaneous voiding compared with plain prilocaine 50 mg. Surgical anesthesia was not different. The incidence of TNS was low.” p. 259

Dijkstra16

2008

Median maximum block at 30 min: Bupivacaine: T7 (range: T4.5 to T9) Articaine: T6 (range: T4.5 to T9.5) Median time to full motor block recovery in minutes: Bupivacaine: 307 (range 225 to 350) Articaine: 101 (range 80 to 129) P < 0.0005 (95% CI not reported) Median time to discharge in minutes Bupivacaine: 380 (range 332 to 431) Articaine: 300 (range 273 to 347) P < 0.0005 No difference in the rates of adverse events between the two groups. One patient receiving articaine and none receiving bupivacaine experienced TNS.

“Spinal anaesthesia with 80 mg of hyperbaric articaine has a shorter duration than a spinal anaesthesia with 15 mg of plain bupivacaine in lower limb surgery of approximately 1 h duration.” p. 104.

Imbelloni9

2008 Median peak block height, range: 15 mg/mL lidocaine: T12, T10 to L2 20 mg/mL lidocaine: T12, T10 to L2 Analgesia duration: 15 mg/mL lidocaine: 50.6 ± 5.3 min 20 mg/mL lidocaine: 56.1 ± 7.2 min

”Hyperbaric lidocaine results in rapid recovery from sensory block and motor blockade. It may have advantages for patients in a day-case setting. No patients complained of TNS after discharge.” p. 856




There were no reports of adverse events or TNS.

Imbelloni10

2008

Median sensory block height at 15 minutes (interquartile range): lidocaine 18 mg: L1 (L3 to T12) lidocaine 24 mg: T11 (T12 to T10) lidocaine 30 mg: T10 (T11 to T10) P < 0.001 (95% CI not reported) Mean analgesia duration: lidocaine 18 mg: 63 ± 9 minutes lidocaine 24 mg: 81 ± 9 minutes lidocaine 30 mg: 89 ± 8 minutes P < 0.001 No hypotension, nausea or vomiting, urine retention, TNS or headache was reported in any patient. There was one case of bradycardia with 24 mg lidocaine, and two with 30 mg (P = NS)

”The smallest dose (3 ml = 18 mg) provides sufficient analgesia with a lesser dispersion and shorter duration.” p. 132

Sell19

2008

No differences in median maximum level of sensory block (T9) between the four groups (P = 0.66, 95% CI not reported) Mean time to full sensory block resolution in minutes (range): Chloroprocaine 35 mg: 111 (96 to 126) Chloroprocaine 40 mg: 108 (95 to 121) Chloroprocaine 45 mg: 128 (116 to 138) Chloroprocaine 50 mg: 134 (123 to 145) 35 mg, 40 mg versus 50 mg, P = 0.005 Median time to discharge in minutes (range): Chloroprocaine 35 mg: 123 (108 to 138) Chloroprocaine 40 mg: 122 (109 to 135) Chloroprocaine 45 mg: 137 (124 to 149) Chloroprocaine 50 mg: 165 (141 to 189) 35 mg, 40 mg versus 50 mg, P = 0.001 No complications or TNS were reported.

“Spinal 2-CP [chloroprocaine], 10 mg/ml 35, 40, 45, and 50 mg provide reliable sensory and motor block for ambulatory surgery, while reducing the dose of 2-CP to 35 and 40 mg resulted in a spinal block of faster ambulation.” p. 695

Boztuğ21

2006

Median peak block height, time to onset: Bupivacaine: T11, 14.3 ± 11.6 min Ropivacaine: T8, 15.4 ± 12.2 min Mean time to motor block offset: Bupivacaine: 269.4 ± 87.8 minutes Ropivacaine: 198.2 ± 52.1 minutes P = 0.015 (95% CI not reported) First urination and discharge times were

”Isobaric ropivacaine 15 mg provided a higher sensory block level and shorter sensorial onset and offset times than did 7.5 mg of isobaric bupivacaine.” p. 521




similar between the two groups. No cases of headache or TNS were reported

Casati14

2006

Median peak sensory block (range): Chloroprocaine 30 mg: T9 (T12 to T4) Chloroprocaine 40 mg: T9 (T12 to T6) Chloroprocaine 50 mg: T9 (T12 to T7) P = 0.388 (95% CI not reported) Median time to spinal block resolution in minutes (range): Chloroprocaine 30 mg: 60 (41 to 98) Chloroprocaine 40 mg: 85 (46 to 141) Chloroprocaine 50 mg: 97 (60 to 169) P = 0.001 Median time to discharge in minutes (range): Chloroprocaine 30 mg: 182 (120 to 267) Chloroprocaine 40 mg: 198 (123 to 271) Chloroprocaine 50 mg: 203 (102 to 394) P = 0.155 Five patients receiving 30 mg and two receiving 40 mg chloroprocaine required analgesic supplementation due to insufficient duration of spinal block (P = 0.014). No serious post-operative complications, side effects, or TNS were recorded.

”40 to 50 mg of plain chloroprocaine 1% provided adequate spinal anesthesia for lower limb outpatient procedures lasting 45 to 60 min. Reducing the dose of 2-chloroprocaine to 30 mg resulted in a spinal block of insufficient duration and had no advantages in terms of home discharge time.” p. 238

Kallio12

2006

Median peak block height, time to onset: Articaine 60 mg: T4 (T9 to T1), 15 min Articaine 84 mg: T4 (T10 to C7), 15 min Articaine 108 mg: T4 (T9 to C3), 15 min Median time to bilateral sensory recovery (min): Articaine 60 mg: 150 (range 75 to 180) Articaine 84 mg: 150 (range 75 to 270) Articaine 108 mg: 150 (range 120 to 270) P = 0.017 (95% CI not reported) Median time to discharge (range): Articaine 60 mg: 251 (range 161 to 427) Articaine 84 mg: 285 (range 192 to 1280) Articaine 108 mg: 279 (range 175 to 437) P = NS Patients receiving a dose of 108 mg had significantly more nausea and vomiting (P = 0.025) and needed more rescue medication for hypotension (P = 0.018) than the other groups. No cases of TNS were reported.

“Hyperbaric articaine 60 and 84 mg resulted in spinal anaesthesia allowing surgery of lower extremities for about 1 h. Recovery was rapid. Use of 108 mg of articaine is not recommended because of frequent extensive cephalad spread of the block , accompanied by arterial hypotension and nausea.” p. 704




Cohort study Hejtmanek

22

2011 Chloroprocaine was the most widely used spinal anesthetic in this practice (503 cases, median/mode dose 40 mg, range 20 to 60 mg), followed by lidocaine (84 cases, median/mode dose 60 mg, range 30 to 100 mg) Mean time to ambulation: Chloroprocaine: 107 ± 24 minutes Lidocaine: 155 ± 40 minutes P < 0.05 (95% CI reported) Mean time to discharge: Chloroprocaine: 171 ± 45 minutes Lidocaine: 224 ± 57 minutes P < 0.05 There were no cases of TNS identified in the study population.

”[T]he time to achievement of discharge criteria was significantly reduced with CP 40 [chloroprocaine 40 mg] vs. lidocaine 60 mg. There have been no reports of perioperative neurologic injury with the introduction of CP as a spinal anesthetic” p. 267

IQR= interquartile range; NS= not significant; TNS= transient neurologic symptoms

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