본문 바로가기
KERD
논문KCI 등재

The impact of ketamine on outcomes in critically ill patients: a systematic review with meta-analysis and trial sequential analysis of randomized controlled trials

Yerkin Abdildin|Karina Tapinova|Assel Nemerenova|Viderman Dmitriy
대한중환자의학회 (The Korean Society Of Critical Care Medicine)|2024.02|Acute and Critical Care|제39권 제1호|pp. 34-46|DOI 10.4266/acc.2023.00829

2

조회

0

다운로드

0

인용

0

참고문헌

키워드

critical careintensive care unitcritical illnessketaminepain management

초록

Background: This meta-analysis aims to evaluate the effects of ketamine in critically ill intensive care unit (ICU) patients.Methods: We searched for randomized controlled trials (RCTs) in PubMed, Scopus, and the Cochrane Library; the search was performed initially in January but was repeated in December of 2023. We focused on ICU patients of any age. We included studies that compared ketamine with other traditional agents used in the ICU. We synthesized evidence using RevMan v5.4 and presented the results as forest plots. We also used trial sequential analysis (TSA) software v. 0.9.5.10 Beta and presented results as TSA plots. For synthesizing results, we used a random-effects model and reported differences in outcomes of two groups in terms of mean difference (MD), standardized MD, and risk ratio with 95% confidence interval. We assessed the risk of bias using the Cochrane RoB tool for RCTs. Our outcomes were mortality, pain, opioid and midazolam requirements, delirium rates, and ICU length of stay.Results: Twelve RCTs involving 805 ICU patients (ketamine group, n=398; control group, n=407) were included in the meta-analysis. The ketamine group was not superior to the control group in terms of mortality (in five studies with 318 patients), pain (two studies with 129 patients), mean and cumulative opioid consumption (six studies with 494 patients), midazolam consumption (six studies with 304 patients), and ICU length of stay (three studies with 270 patients). However, the model favored the ketamine group over the control group in delirium rate (four studies with 358 patients). This result is significant in terms of conventional boundaries (alpha=5%) but is not robust in sequential analysis. The applicability of the findings is limited by the small number of patients pooled for each outcome.Conclusions: Our meta-analysis did not demonstrate differences between ketamine and control groups regarding any outcome except delirium rate, where the model favored the ketamine group over the control group. However, this result is not robust as sensitivity analysis and trial sequential analysis suggest that more RCTs should be conducted in the future.

Abstract

Background: This meta-analysis aims to evaluate the effects of ketamine in critically ill intensive care unit (ICU) patients.Methods: We searched for randomized controlled trials (RCTs) in PubMed, Scopus, and the Cochrane Library; the search was performed initially in January but was repeated in December of 2023. We focused on ICU patients of any age. We included studies that compared ketamine with other traditional agents used in the ICU. We synthesized evidence using RevMan v5.4 and presented the results as forest plots. We also used trial sequential analysis (TSA) software v. 0.9.5.10 Beta and presented results as TSA plots. For synthesizing results, we used a random-effects model and reported differences in outcomes of two groups in terms of mean difference (MD), standardized MD, and risk ratio with 95% confidence interval. We assessed the risk of bias using the Cochrane RoB tool for RCTs. Our outcomes were mortality, pain, opioid and midazolam requirements, delirium rates, and ICU length of stay.Results: Twelve RCTs involving 805 ICU patients (ketamine group, n=398; control group, n=407) were included in the meta-analysis. The ketamine group was not superior to the control group in terms of mortality (in five studies with 318 patients), pain (two studies with 129 patients), mean and cumulative opioid consumption (six studies with 494 patients), midazolam consumption (six studies with 304 patients), and ICU length of stay (three studies with 270 patients). However, the model favored the ketamine group over the control group in delirium rate (four studies with 358 patients). This result is significant in terms of conventional boundaries (alpha=5%) but is not robust in sequential analysis. The applicability of the findings is limited by the small number of patients pooled for each outcome.Conclusions: Our meta-analysis did not demonstrate differences between ketamine and control groups regarding any outcome except delirium rate, where the model favored the ketamine group over the control group. However, this result is not robust as sensitivity analysis and trial sequential analysis suggest that more RCTs should be conducted in the future.

참고문헌 (52)

  1. Wheeler KE, "Adjuvant analgesic use in the critically ill : a systematic review and meta-analysis", Crit Care Explor, 2, pp.e0157~ (2020)
  2. Brinck EC, "Perioperative intravenous ketamine for acute postoperative pain in adults", Cochrane Database Syst Rev, 12, pp.CD012033~ (2018)
  3. Chan K, "Impact of ketamine on analgosedative consumption in critically ill patients : a systematic review and meta-analysis", Ann Pharmacother, 56, pp.1139~1158 (2022)
  4. Hurth KP, "The reemergence of ketamine for treatment in critically ill adults", Crit Care Med, 48, pp.899~911 (2020)
  5. Wang H, "Sedative drugs used for mechanically ventilated patients in intensive care units : a systematic review and network meta-analysis", Curr Med Res Opin, 35, pp.435~446 (2019)
  6. Koo BN, "Continuous infusion of ketamine in mechanically ventilated patient in septic shock with status asthmaticus", Korean J Crit Care Med, 15, pp.108~112 (2000)
  7. Kim TH, "Comparison of the efficacy between ketamine and morphine on sedation and analgesia in patients with mechanical ventilation", Korean J Crit Care Med, 15, pp.82~87 (2000)
  8. Jabre P, "Etomidate versus ketamine for rapid sequence intubation in acutely ill patients : a multicentre randomised controlled trial", Lancet, 374, pp.293~300 (2009)
  9. Hughes S, "Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. BET 3: is ketamine a viable induction agent for the trauma patient with potential brain injury", Emerg Med J, 28, pp.1076~1077 (2011)
  10. Knack SK, "The effect of ketamine versus etomidate for rapid sequence intubation on maximum sequential organ failure assessment score : a randomized clinical trial", J Emerg Med, 65, pp.e371~e382 (2023)
  11. Holland D, "Prehospital sedation with ketamine vs. midazolam: repeat sedation, intubation, and hospital outcomes", Am J Emerg Med, 38, pp.1748~1753 (2020)
  12. Panzer O, "Pharmacology of sedative-analgesic agents : dexmedetomidine, remifentanil, ketamine, volatile anesthetics, and the role of peripheral Mu antagonists", Anesthesiol Clin, 29, pp.587~605 (2011)
  13. Buchheit JL, "Impact of low-dose ketamine on the usage of continuous opioid infusion for the treatment of pain in adult mechanically ventilated patients in surgical intensive care units", J Intensive Care Med, 34, pp.646~651 (2019)
  14. Hudetz JA, "Ketamine attenuates delirium after cardiac surgery with cardiopulmonary bypass", J Cardiothorac Vasc Anesth, 23, pp.651~657 (2009)
  15. Smischney NJ, "Ketamine", propofol admixture(ketofol)is associated with improved hemodynamics as an induction agent : a randomized, controlled trial, 2012, pp.73, 94~101
  16. Zeiler FA, "The ketamine effect on ICP in traumatic brain injury", Neurocrit Care, 21, pp.163~173 (2014)
  17. Hudetz JA, "Neuroprotection by ketamine : a review of the experimental and clinical evidence", J Cardiothorac Vasc Anesth, 24, pp.131~142 (2010)
  18. Chang LC, "The emerging use of ketamine for anesthesia and sedation in traumatic brain injuries", CNS Neurosci Ther, 19, pp.390~395 (2013)
  19. Kumar A, "Comeback of ketamine : resurfacing facts and dispelling myths", Korean J Anesthesiol, 74, pp.103~114 (2021)
  20. Von der Brelie C, "Sedation of patients with acute aneurysmal subarachnoid hemorrhage with ketamine is safe and might influence the occurrence of cerebral infarctions associated with delayed cerebral ischemia", World Neurosurg, 97, pp.374~382 (2017)
  21. Erstad BL, "Ketamine for analgosedation in critically ill patients", J Crit Care, 35, pp.145~149 (2016)
  22. Manasco AT, "Ketamine sedation in mechanically ventilated patients : a systematic review and meta-analysis", J Crit Care, 56, pp.80~88 (2020)
  23. Perbet S, "Low doses of ketamine reduce delirium but not opiate consumption in mechanically ventilated and sedated ICU patients : a randomised double-blind control trial", Anaesth Crit Care Pain Med, 37, pp.589~595 (2018)
  24. Hovaguimian F, "Intraoperative ketamine administration to prevent delirium or postoperative cognitive dysfunction : a systematic review and meta-analysis", Acta Anaesthesiol Scand, 62, pp.1182~1193 (2018)
  25. Mion G, "Ketamine infusions for sedation in ICU", Anaesth Crit Care Pain Med, 38, pp.397~398 (2019)
  26. Perbet S, "Ketamine infusion for sedation in ICU, response to Dr Mion", Anaesth Crit Care Pain Med, 38, pp.399~ (2019)
  27. Viderman D, "Effect of ketamine on postoperative neurocognitive disorders : a systematic review and meta-analysis", J Clin Med, 12, pp.4314~ (2023)
  28. Viderman D, "Postoperative delirium and cognitive dysfunction after general and regional anesthesia : a systematic review and meta-analysis", J Clin Med, 12, pp.3549~ (2023)
  30. Thorlund K, "Trial sequential analysis(TSA)", Copenhagen Trial Unit, ~ (2011)
  31. Luo D, "Optimally estimating the sample mean from the sample size, median, mid-range, and", or mid-quartile range, 2018, pp.27, 1785~1805
  32. Wan X, "Estimating the sample mean and standard deviation from the sample size, median, range and", or interquartile range, 2014, pp.14, 135~
  33. "RevMan" (2023)[URL]
  34. Kang H, "Trial sequential analysis : novel approach for meta-analysis", Anesth Pain Med(Seoul), 16, pp.138~150 (2021)
  35. Sanfilippo F, "Trial sequential analysis : the evaluation of the robustness of meta-analyses findings and the need for further research", EuroMediterranean Biomed J, 16, pp.104~107 (2021)
  36. Wetterslev J, "Trial sequential analysis may establish when firm evidence is reached in cumulative meta-analysis", J Clin Epidemiol, 61, pp.64~75 (2008)
  37. De Cassai A, "Trial sequential analysis : plain and simple", Korean J Anesthesiol, 74, pp.363~365 (2021)
  38. Castellini G, "Assessing imprecision in Cochrane systematic reviews : a comparison of GRADE and Trial Sequential Analysis", Syst Rev, 7, pp.110~ (2018)
  39. Higgins JP, "The Cochrane Collaboration's tool for assessing risk of bias in randomised trials", BMJ, 343, pp.d5928~ (2011)
  40. Amer M, "Adjunctive ketamine for sedation in critically ill mechanically ventilated patients : an active-controlled, pilot, feasibility clinical trial", J Intensive Care, 9, pp.54~ (2021)
  41. Anwar S, "Prolonged perioperative use of pregabalin and ketamine to prevent persistent pain after cardiac surgery", Anesthesiology, 131, pp.119~131 (2019)
  42. Bawazeer M, "Adjunct low-dose ketamine infusion vs standard of care in mechanically ventilated critically ill patients at a Tertiary Saudi Hospital(ATTAINMENT Trial) : study protocol for a randomized, prospective, pilot, feasibility trial", Trials, 21, pp.288~ (2020)
  43. Christ G, "Adverse cardiovascular effects of ketamine infusion in patients with catecholamine-dependent heart failure", Anaesth Intensive Care, 25, pp.255~259 (1997)
  44. Garner O, "Impact of ketamine as an adjunct sedative in acute respiratory distress syndrome due to COVID-19 Pneumonia", Respir Med, 189, pp.106667~ (2021)
  45. Kolenda H, "Ketamine for analgosedative therapy in intensive care treatment of head-injured patients", Acta Neurochir(Wien), 138, pp.1193~1199 (1996)
  46. Quisilema-Cadena JM, "Comparación de dos esquemas de sedoanalgesia : Hermanos Ameijeiras", Revista Mexicana Anestesiología, 40, pp.155~161 (2017)
  47. Schmittner MD, "Effects of fentanyl and S(+)-ketamine on cerebral hemodynamics, gastrointestinal motility, and need of vasopressors in patients with intracranial pathologies : a pilot study", J Neurosurg Anesthesiol, 19, pp.257~262 (2007)
  48. Guillou N, "The effects of small-dose ketamine on morphine consumption in surgical intensive care unit patients after major abdominal surgery", Anesth Analg, 97, pp.843~847 (2003)
  49. Minoshima R, "Intra-and postoperative low-dose ketamine for adolescent idiopathic scoliosis surgery : a randomized controlled trial", Acta Anaesthesiol Scand, 59, pp.1260~1268 (2015)
  50. Dzierba AL, "Ketamine use in sedation management in patients receiving extracorporeal membrane oxygenation", Intensive Care Med, 42, pp.1822~1823 (2016)
  51. Bourgoin A, "Safety of sedation with ketamine in severe head injury patients : comparison with sufentanil", Crit Care Med, 31, pp.711~717 (2003)
  52. Bourgoin A, "Effects of sufentanil or ketamine administered in target-controlled infusion on the cerebral hemodynamics of severely brain-injured patients", Crit Care Med, 33, pp.1109~1113 (2005)

관련 논문AI추천

Prevention and management of delirium in critically ill adult patients in the intensive care unit: a review based on the 2018 PADIS guidelinesHeung Bum Lee, Seung Yong Park대한중환자의학회 · Acute and Critical Care2019 · 제34권 제2호Comparison of Morphine and Remifentanil on the Duration of Weaning from Mechanical Ventilation강현희, 곽상현, 이상학, 이성헌, 이영주, 이재명, 임재민, 임채만, 정미애대한중환자의학회 · Acute and Critical Care2014 · 제29권 제4호2021 KSCCM clinical practice guidelines for pain, agitation, delirium, immobility, and sleep disturbance in the intensive care unit서이준, 이학재, 하은진, 하태순대한중환자의학회 · Acute and Critical Care2022 · 제37권 제1호Comparison of Morphine and Remifentanil on the Duration of Weaning from Mechanical Ventilation강현휘, 곽상현, 이상학, 이성헌, 이영주, 이재명, 임재민, 임채만, 정미애대한중환자의학회 · Acute and Critical Care2016 · 제31권 제4호중환자에서 Dexmedetomidine의 Opioid-Sparing Effect를 고려한 Remifentanil 용량 조절김형숙, 이연주, 이은숙, 이정화, 조영재, 한수정한국병원약사회 · 병원약사회지2014 · 제31권 제4호The effects of environmental interventions for delirium in critically ill surgical patients이학재, 정윤중, 최낙준, 홍석경대한중환자의학회 · Acute and Critical Care2023 · 제38권 제4호

이 간행물의 다른 논문 (23건)

Liberation from mechanical ventilation in critically ill patients: Korean Society of Critical Care Medicine Clinical Practice Guidelines박소영, 오동규, 정인석, 박성훈, 장유진, 이학재, 서지영, 하태순, 심윤수, 홍석경pp. 1-23Brain–computer interface in critical care and rehabilitation김성필, 신세영, 오은서pp. 24-33Prolonged intensive care: muscular functional, and nutritional insights from the COVID-19 pandemicÁngel Augusto Pérez-Calatayud, Miguel Ángel Martínez-Camacho, Robert Alexander Jones-Baro, Alberto Gómez-González, Dalia Sahian Lugo-García, Pía Carolina Gallardo Astorga, Andrea Melo-Villalobos, Bárbara Kassandra Gonzalez-Rodriguezpp. 47-60Comparison of preoxygenation with a high-flow nasal cannula and a simple face mask before intubation in Korean patients with head and neck cancer최성수, 장희윤, 조준영, 김욱종, 윤정필, Seung-Woo Kupp. 61-69Prevalence of extracorporeal blood purification techniques in critically ill patients before and during the COVID-19 pandemic in EgyptHanaa I. Rady, Aya Osama Mohammedpp. 70-77
원문 보기