Risk factors for opioid-induced respiratory depression in surgical patients: a systematic review and meta-analyses

Kapil Gupta, Mahesh Nagappa, Arun Prasad, Lusine Abrahamyan, Jean Wong, Toby N Weingarten, Frances Chung, Kapil Gupta, Mahesh Nagappa, Arun Prasad, Lusine Abrahamyan, Jean Wong, Toby N Weingarten, Frances Chung

Abstract

Objective: This systematic review and meta-analysis aim to evaluate the risk factors associated with postoperative opioid-induced respiratory depression (OIRD).

Design: Systematic review and meta-analysis.

Data sources: PubMed-MEDLINE, MEDLINE in-process, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, PubMed and Clinicaltrials.gov (January 1946 to November 2017).

Eligibility criteria: The inclusion criteria were: (1) adult patients 18 years or older who were administered opioids after surgery and developed postoperative OIRD (OIRD group); (2) all studies which reported both OIRD events and associated risk factors; (3) all studies with reported data for each risk factor on patients with no OIRD (control group) and (4) published articles in English language.

Data analysis: We used a random effects inverse variance analysis to evaluate the existing evidence of risk factors associated with OIRD. Newcastle-Ottawa scale scoring system was used to assess quality of study.

Results: Twelve observational studies were included from 8690 citations. The incidence of postoperative OIRD was 5.0 cases per 1000 anaesthetics administered (95% CI: 4.8 to 5.1; total patients: 841 424; OIRD: 4194). Eighty-five per cent of OIRD occurred within the first 24 hours postoperatively. Increased risk for OIRD was associated with pre-existing cardiac disease (OIRD vs control: 42.8% vs 29.6%; OR: 1.7; 95% CI: 1.2 to 2.5; I2: 0%; p<0.002), pulmonary disease (OIRD vs control: 17.8% vs 10.3%; OR: 2.2; 95% CI: 1.3 to 3.6; I2: 0%; p<0.001) and obstructive sleep apnoea (OIRD vs control: 17.9% vs 16.5%; OR: 1.4; 95% CI: 1.2 to 1.7; I2: 31%; p=0.0003). The morphine equivalent daily dose of the postoperative opioids was higher in the OIRD group than in the control; (24.7±14 mg vs 18.9±13.0 mg; mean difference: 2.8; 95% CI: 0.4 to 5.3; I2: 98%; p=0.02). There was no significant association between OIRD and age, gender, body mass index or American Society of Anesthesiologists physical status.

Conclusion: Patients with cardiac, respiratory disease and/or obstructive sleep apnoea were at increased risk for OIRD. Patients with postoperative OIRD received higher doses of morphine equivalent daily dose.

Keywords: anaesthesia; opioids; postoperative complications; respiratory depression; risk factors; surgery.

Conflict of interest statement

Competing interests: JW reports grants from the Ontario Ministry of Health and Long-Term Care, Anesthesia Patient Safety Foundation and Acacia Pharma outside of the submitted work. FC reports research support from the Ontario Ministry of Health and Long-Term Care, University Health Network Foundation, Acacia Pharma, Medtronic grants to institution outside of the submitted work, up-to-date royalties, STOP-Bang proprietary to University Health Network. TNW currently serves as a consultant to Medtronic in the role as chairman of the Clinical Endpoint Committee for the Prodigy Trial; has received unrestricted investigator-initiated grants from Merck (active) and Baxter (completed), and research support from Respiratory Motion (study equipment) and research support from Respiratory Motion (study equipment).

© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Flow diagram of search strategy used for systematic review and meta-analysis.
Figure 2
Figure 2
Meta-analysis evaluating the risk factors for respiratory events between OIRD and control groups in patients undergoing surgery. The pooled OR for each risk factor is plotted along with the 95% CI summarises the effect size using the inverse variance random effects model. Age and BMI represented as mean±SD. ASA, American Society of Anesthesiologists; BMI, body mass index; I2, heterogeneity; OIRD, opioid-induced respiratory depression; OSA, obstructive sleep apnoea.
Figure 3
Figure 3
Meta-analysis evaluating the risk factors for respiratory events between OIRD and control groups in patients undergoing surgery. The pooled OR for each risk factor is plotted along with the 95% CI summarises the effect size using the inverse variance random effects model. I2, heterogeneity; LOS, length of hospital stay represented as mean±SD; MEDD, morphine equivalent daily dose; OIRD, opioid-induced respiratory depression; PCA, patient-controlled analgesia.

References

    1. Frasco PE, Sprung J, Trentman TL. The impact of the joint commission for accreditation of healthcare organizations pain initiative on perioperative opiate consumption and recovery room length of stay. Anesth Analg 2005;100:162–8. 10.1213/01.ANE.0000139354.26208.1C
    1. Kessler ER, Shah M, Gruschkus SK, et al. . Cost and quality implications of opioid-based postsurgical pain control using administrative claims data from a large health system: opioid-related adverse events and their impact on clinical and economic outcomes. Pharmacotherapy 2013;33:383–91. 10.1002/phar.1223
    1. Rosenfeld DM, Betcher JA, Shah RA, et al. . Findings of a naloxone database and its utilization to improve safety and education in a tertiary care medical center. Pain Pract 2016;16:327–33. 10.1111/papr.12277
    1. Weingarten TN, Chong EY, Schroeder DR, et al. . Predictors and outcomes following naloxone administration during Phase I anesthesia recovery. J Anesth 2016;30:116–22. 10.1007/s00540-015-2082-0
    1. Taylor S, Kirton OC, Staff I, et al. . Postoperative day one: a high risk period for respiratory events. Am J Surg 2005;190:752–6. 10.1016/j.amjsurg.2005.07.015
    1. Etches RC. Respiratory depression associated with patient-controlled analgesia: a review of eight cases. Can J Anaesth 1994;41:125–32. 10.1007/BF03009805
    1. Weingarten TN, Jacob AK, Njathi CW, et al. . Multimodal analgesic protocol and postanesthesia respiratory depression during phase i recovery after total joint arthroplasty. Reg Anesth Pain Med 2015;40:330–6. 10.1097/AAP.0000000000000257
    1. Weingarten TN, Herasevich V, McGlinch MC, et al. . Predictors of delayed postoperative respiratory depression assessed from naloxone administration. Anesth Analg 2015;121:422–9. 10.1213/ANE.0000000000000792
    1. Khelemsky Y, Kothari R, Campbell N, et al. . Incidence and demographics of post-operative naloxone administration: a 13-year experience at a major tertiary teaching institution. Pain Physician 2015;18:E827–9.
    1. Lee LA, Caplan RA, Stephens LS, et al. . Postoperative opioid-induced respiratory depression: a closed claims analysis. Anesthesiology 2015;122:659–65. 10.1097/ALN.0000000000000564
    1. Ramachandran SK, Haider N, Saran KA, et al. . Life-threatening critical respiratory events: a retrospective study of postoperative patients found unresponsive during analgesic therapy. J Clin Anesth 2011;23:207–13. 10.1016/j.jclinane.2010.09.003
    1. Overdyk FJ, Carter R, Maddox RR, et al. . Continuous oximetry/capnometry monitoring reveals frequent desaturation and bradypnea during patient-controlled analgesia. Anesth Analg 2007;105:412–8. 10.1213/01.ane.0000269489.26048.63
    1. Shapiro A, Zohar E, Zaslansky R, et al. . The frequency and timing of respiratory depression in 1524 postoperative patients treated with systemic or neuraxial morphine. J Clin Anesth 2005;17:537–42. 10.1016/j.jclinane.2005.01.006
    1. Gordon DB, Pellino TA. Incidence and characteristics of naloxone use in postoperative pain management: a critical examination of naloxone use as a potential quality measure. Pain Manag Nurs 2005;6:30–6. 10.1016/j.pmn.2004.12.003
    1. Moher D, Liberati A, Tetzlaff J, et al. . Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 2009;151:264–9. 10.7326/0003-4819-151-4-200908180-00135
    1. Wells GSB, O’Connell D, Peterson J, et al. . The Newcastle-Ottawa Scale (NOS) for assessing the quality if nonrandomized studies in meta-analyses Ottawa. 2014. .
    1. Stroup DF, Berlin JA, Morton SC, et al. . Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000;283:2008–12.
    1. Morris TA, Gay PC, MacIntyre NR, et al. . Respiratory compromise as a new paradigm for the care of vulnerable hospitalized patients. Respir Care 2017;62:497–512. 10.4187/respcare.05021
    1. Ramachandran SK, Pandit J, Devine S, et al. . Postoperative respiratory complications in patients at risk for obstructive sleep apnea: a single-institution cohort study. Anesth Analg 2017;125:272–9. 10.1213/ANE.0000000000002132
    1. Zedler BK, Saunders WB, Joyce AR, et al. . Validation of a screening risk index for serious prescription opioid-induced respiratory depression or overdose in a US commercial health plan claims database. Pain Med 2018;19:68–78. 10.1093/pm/pnx009
    1. Singh M, Liao P, Kobah S, et al. . Proportion of surgical patients with undiagnosed obstructive sleep apnoea. Br J Anaesth 2013;110:629–36. 10.1093/bja/aes465
    1. Nagappa M, Patra J, Wong J, et al. . Association of STOP-bang questionnaire as a screening tool for sleep apnea and postoperative complications: a systematic review and bayesian meta-analysis of prospective and retrospective cohort studies. Anesth Analg 2017;125:1301–8. 10.1213/ANE.0000000000002344
    1. Nagappa M, Ho G, Patra J, et al. . Postoperative outcomes in obstructive sleep apnea patients undergoing cardiac surgery: a systematic review and meta-analysis of comparative studies. Anesth Analg 2017;125:2030–7. 10.1213/ANE.0000000000002558
    1. Subramani Y, Singh M, Wong J, et al. . Understanding phenotypes of obstructive sleep apnea. Anesthesia & Analgesia 2017;124:179–91. 10.1213/ANE.0000000000001546
    1. Lam KK, Kunder S, Wong J, et al. . Obstructive sleep apnea, pain, and opioids: is the riddle solved? Curr Opin Anaesthesiol 2016;29:134–40. 10.1097/ACO.0000000000000265
    1. Correa D, Farney RJ, Chung F, et al. . Chronic opioid use and central sleep apnea: a review of the prevalence, mechanisms, and perioperative considerations. Anesth Analg 2015;120:1273–85. 10.1213/ANE.0000000000000672
    1. Chung F, Memtsoudis SG, Ramachandran SK, et al. . Society of anesthesia and sleep medicine guidelines on preoperative screening and assessment of adult patients with obstructive sleep apnea. Anesth Analg 2016;123:452–73. 10.1213/ANE.0000000000001416
    1. Subramani Y, Nagappa M, Wong J, et al. . Death or near-death in patients with obstructive sleep apnoea: a compendium of case reports of critical complications. Br J Anaesth 2017;119:885–99. 10.1093/bja/aex341
    1. Chung F, Liao P, Elsaid H, et al. . Factors associated with postoperative exacerbation of sleep-disordered breathing. Anesthesiology 2014;120:299–311. 10.1097/ALN.0000000000000041
    1. Blake DW, Yew CY, Donnan GB, et al. . Postoperative analgesia and respiratory events in patients with symptoms of obstructive sleep apnoea. Anaesth Intensive Care 2009;37:720–5.
    1. George JA, Lin EE, Hanna MN, et al. . The effect of intravenous opioid patient-controlled analgesia with and without background infusion on respiratory depression: a meta-analysis. J Opioid Manag 2010;6:47–54. 10.5055/jom.2010.0004
    1. Cavalcante AN, Sprung J, Schroeder DR, et al. . Multimodal analgesic therapy with gabapentin and its association with postoperative respiratory depression. Anesth Analg 2017;125:141–6. 10.1213/ANE.0000000000001719
    1. Deljou A, Hedrick SJ, Portner ER, et al. . Pattern of perioperative gabapentinoid use and risk for postoperative naloxone administration. Br J Anaesth 2018;120:798–806. 10.1016/j.bja.2017.11.113
    1. Overdyk FJ, Dowling O, Marino J, et al. . Association of opioids and sedatives with increased risk of in-hospital cardiopulmonary arrest from an administrative database. PLoS One 2016;11:11:e0150214 10.1371/journal.pone.0150214
    1. Park TW, Saitz R, Ganoczy D, et al. . Benzodiazepine prescribing patterns and deaths from drug overdose among US veterans receiving opioid analgesics: case-cohort study. BMJ 2015;350:h2698 10.1136/bmj.h2698
    1. Weingarten TN, Warner LL, Sprung J. Timing of postoperative respiratory emergencies: when do they really occur? Curr Opin Anaesthesiol 2017;30:156–62. 10.1097/ACO.0000000000000401
    1. Chung F, Liao P, Yang Y, et al. . Postoperative sleep-disordered breathing in patients without preoperative sleep apnea. Anesth Analg 2015;120:1214–24. 10.1213/ANE.0000000000000774
    1. Chung F, Liao P, Yegneswaran B, et al. . Postoperative changes in sleep-disordered breathing and sleep architecture in patients with obstructive sleep apnea. Anesthesiology 2014;120:287–98. 10.1097/ALN.0000000000000040
    1. Horlocker TT, Burton AW, Connis RT, et al. . Practice guidelines for the prevention, detection, and management of respiratory depression associated with neuraxial opioid administration. Anesthesiology 2009;110:218–30. 10.1097/ALN.0b013e31818ec946
    1. Khanna AK, Khanna AK, Khanna AK. Respiratory depression on the wards: why better monitoring may be the answer? Anesthesiology - Open Journal 2017;2:9–11. 10.17140/AOJ-2-109
    1. Borenstein M, Higgins JP, Hedges LV, et al. . Basics of meta-analysis: I2 is not an absolute measure of heterogeneity. Res Synth Methods 2017;8:5–18. 10.1002/jrsm.1230

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe