Respiratory Depression in the Early Postoperative Period. Toby N Weingarten, MD Mayo Clinic Professor Anesthesiology
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1 Respiratory Depression in the Early Postoperative Period Toby N Weingarten, MD Mayo Clinic Professor Anesthesiology
2 Conflicts of Interest Medtronic Chair of CEC Committee for PRODIGY Trial Merck Investigator initiated unrestricted research grant Manufacturer of sugammadex Previous Research Support Baxter Healthcare Investigator initiated unrestricted research grant Manufacturer of Desflurane and Scopolamine patch Respiratory Motion Material support of research study Manufacturer of ExSpiron monitor SASM
3 Learning Objectives: Incidence of postoperative hypercarbic respiratory depression Temporal relationship between end of surgery and development of respiratory depression Review risk factors for respiratory depression Review implications and risk factors for respiratory depression in the PACU
4 Postoperative Respiratory Failure Decreased defusion - ARDS - Pneumonia - Atelectasis Decreased ventilation - Weakness - Drive Failure to Rescue Anoxic Brain Injury Death
5 Hypercarbic Respiratory Failure Arrests from decreased respiratory drive Multifactorial Medications 63% Increase! Underlying comorbidities Frasco P, Sprung J, Trentman T, A&A 2005 Hamlin RJ Acta Chir Belg. 2013
6 Rate of serious OIRD Study Measure Number Rate Rosenfeld 2016 Naloxone 108/28, % Weingarten 2015 Naloxone 134/84, % Khelemsk 2015 Naloxone 433/442, % Ramachandran 2011 Naloxone + CPR 44/87, % Gordon 2005 Naloxone 56/10, % Total 775/ % 2015 ASA Closed Claim Postoperative OIRD Median payout of $216,750 Gupta K, abstract SASM 2017 Lee LA, Anesthesiology 2015
7 Postoperative Hypoxemia Very Common CCF 1250 non-cv patients SPO2 monitored 21% 10 m/h SpO 2 <90% 8% 20 m/h SpO 2 <90% 8% 5 m/h SpO 2 <85% SpO 2 <90%, 37% episode > 1 hr 11% episode > 6 hr SpO 2 <80%, 3% episode > 0.5 hr Nursing records missed 90% of cases of SPO2 <90% 1 hour! Sun Z A&A 2015
8 Hypoxemia is underappreciated Intermittent Nursing Checks Nursing records missed 90% of cases! 85% 91% Manually measured APSF rates intermittent nursing checks Low-moderate sensitivity, specificity and reliability, Slow response times Taenzer A 2014, APSF Fall 2011 newsletter SPO2 is 6.5% ( %) higher than automated systems. WAKE UP EFFECT
9 Time of greatest risk ASA Closed Claims of postoperative opioid-induced respiratory depression 88% happened within 1 st postoperative day 25% 20% 15% 10% 5% 0% Lee LA 2015, Weingarten 2015, Weingarten 2016
10 7 6 Early Events (< 4 hrs) Hour of the Day Later Events Ramachandran 2011, Weingarten Hour of the Day
11 Following Vital Sign Checks Many respiratory events in the closed claim analysis happened shortly after a reassuring vital sign check! SPO2 increases with manual vital sign checks 6.5% ( %) APSF rates intermittent nursing checks Low-moderate sensitivity, specificity and reliability, Slowresponse times Lee 2015, Taenzer A 2014, APSF Fall 2011 newsletter
12 OSA CV Patient Factors: NARCAN ADMINISTRATION < 48 HOURS OF PACU DISCHARGE 2.44 ( ) 90% cases undiagnosed 20% adult surgical patients 2.56 ( ) CNS 4.05 ( ) Weingarten 2015, Young T 1997, Singh M 2013
13 Three Emerging Phenotypes Variable Narcan N = 128 Control N = 256 OR (95% C.I.) p Age, years 61.8 ± ± 14.4 Male 46 (35.9) 92 (35.9) BMI 29.0 ± ± (0.98, 1.04) OSA 47 (36.7) 55 (21.5) 2.12 (1.33, 3.38) Charlson score 5 [2, 7] 4 [2, 7] 1.03 (0.96, 1.10) Disability 67 (52.3) 85 (33.2) 2.21 (1.43, 3.41) <0.001 Home Use Opioids 42 (52.3) 57 (22.3) 1.71 (1.06, 2.73) Benzodiazepines 25 (19.5) 21 (8.2) 2.72 (1.45, 5.01) Gabapentinoids 39 (30.5) 27 (10.6) 3.72 (2.15, 6.43) <0.001 *Deljou SASM abstract 2017
14 SURGICAL FACTORS surrogates for bigger surgeries Longer duration 7% increased odds per half hour Long-acting vs. short-acting opioid OR 2.48 ( ) Weingarten 2015
15 PERIOPERATIVE FACTORS Type of Surgery 35% 30% 25% TOTAL NARCAN 20% 15% 10% 5% 0% Ortho General Uro/Gyn Neuro ENT Thoracic Vasc
16 PACU COURSE
17 Mayo Clinic Discharge Criteria a) Motor Activity 2 Active motion 1 Weak motion 0 No motion b) Respiration 2 Coughs on command 1 Maintains airway without support 0 Requires airway maintenance c) Systolic 2 ± 20 mmhg preanesthetic level 1 ± mmhg 0 50 mmhg d) Consciousness 2 Fully awake or easily aroused 1 Responds to stimulus 0 No response or absent protective reflexes e) Oxygen saturation 2 Sat 93% (or preop) without O 2 1 Sat 93% (or preop) with O 2 0 Sat 93% (or preop) with O 2 Patient can be discharged with score 8 unless there is a 0 in any category
18 Respiratory Specific Events Hypoventilation 3 episodes < 8 breaths per minute Apnea 1 episode 10 seconds Desaturations 3 episodes Pulse Ox < 90% or preop saturation with or without O 2 Pain Sedation Mismatch 1 episode RASS < -1 and Pain Score > 5 Gali 2007, Gali 2009
19 Mayo Respiratory Events
20 Seet E 2010
21 Algorithm for OSA patient triage CPAP Known OSA Suspected OSA Non-compliant with CPAP Severe (AHI > 30) Recurrent respiratory events DELAY DELAY Seet E 2010 Consider CPAP Considered advanced monitoring
22 OSA and PACU Respiratory Depression OR 5.11 ( ) of receiving naloxone after PACU Discharge PACU naloxone administration had OR 3.39, 95 % CI , P < for adverse events Gali 2009, Weingarten 2015, Weingarten 2016
23 ICU Admissions and PACU Respiratory Depression Surgery Respiratory Events ICU Admissions P Event Event Free TJA (n=11,970) 2,836 (23.4%) 189 (6.8%) 121 (1.3%) <0.001 Laparoscopic > 90 (n=8,567) 1,311 (15.3%) 101 (7.7%) 407 (5.6%) Weingarten 2015, Cavalcante 2017
24 PACU episodes of respiratory depression fits into early warning theory Taenzer Anesthesiology 2011
25 Hypoxemia in PACU 137,757 patients 2007 Vanderbilt Hypoxemia < 90% for 2 minutes 11% patients had a hypoxic event 66% only had 1 event 70% had event > 30 minutes 0.1% reintubated 63% > 30 minutes Epstein RH, Dexter F A&A, 2014
26 Rates of PACU Respiratory Depression at Mayo Population Hospital Rate Hip/Knee TJA (6,467) A 31% Laparoscopic >90 min (5,412) A 19% Laparoscopic > 90 min (3,258) B 9% General Surgery (3,137) B 8% Laparoscopic Bariatric (781) B 4% Weingarten et al, BMC-A 2015, Obesity Surgery 2015, RAPM 2015, A&A 2017
27 MIN Practice Differences Hospital A B ISOFLURANE 53% 29% MIDAZOLAM 78% 37% GABAPENTIN 26% 1% RMH A SMH B Time to DC Criteria Met n = 8,670
28 PACU Respiratory Depression Risk Factors Patient Older Age Lower BMI OSA not a factor Anesthetic Opioids Non-opioid analgesics Gabapentinoids Ketamine Volatiles NMBD
29 Opioids Higher doses = greater risk 1-2% increase risk per 1 IVME mg Potentiated by midazolam with induction Preop sustained release oxycodone for TJA 10 mg dose = OR (1.030,1.347) 20 mg dose = (1.068, 1.566) Weingarten et al, BMC-A 2015, RAPM 2015, A&A 2017
30 Sustained Release Oxycodone T max 157±64 minutes Mean time of surgery was 121±49 minutes Mandema JW Br J Clin Pharmacol 1996; 42:747
31 Gabapentinoids Knee/Hip TJA (n = 6,467) 300 mg = [0.982, 1.505] 600 mg = [1.255, 1.687] Laparoscopic > 90 minutes (n = 8,670) 1.47 [1.22, 1.76] Naloxone < 48 hours of surgery* Continuation of home gabapentinoids OR 6.3 (2.38, 16.66), P=0.001 Weingarten RAPM 2015, Cavalcante A&A 2017, *Deljou SASM abstract 2017
32 Gabapentinoids & Respiratory Depression? 12 ASA I yo DB cross over Pregabalin vs Placebo 150mg 13 hr and 1 hr before study Remifentanil infusion vs Placebo Myhre M, Anesthesiology 2016
33 Gabapentin, opioids, and the risk of opioid related death: A population-based nested case ± control study 1,256 regular opioid users who died of opioid-related causes were matched 4:1 of regular opioid users who did not die of opioid-related causes Gomes T PLoS Med 2017
34 Hip/Knee TJA Volatiles Desflurane = [0.718, 0.979] Laparoscopic > 90 minutes* Isoflurane = 1.31 [1.15, 1.50] Open Eyes Consciousness Recovered Weingarten RAPM 2015, Eger & Shafer AA 2005, *Submitted to BMC Research Notes 2017
35 Change in anesthetic management Comparison 2 six month epochs Epoch I Epoch II 70 Percentage Desflurane Isoflurane Sevoflurane Propfol Mixed* MidazolamTriple antiemetics Anesthetic Management Weingarten BMCA2015
36 Median Decrease in PACU stay Respiratory depression decreased 7.8% to 5.1%, P< % decrease [44, 90] minutes 72 [50, 102] minutes 14% Decrease! Epoch I Epoch II Weingarten BMCA2015
37 Postoperative Respiratory Depression Risks Lessons from Inpatient Observations Develop early postoperative period Patient factors: OSA, CNS/CV disease or frailty Tolerance Surgical factors Anesthetic factors: Longer acting anesthetics Sedating medications
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