Patient Safety Tip of the Week

May 17, 2011

Opioid-Induced Respiratory Depression – Again!



A year ago we discussed the issue of respiratory depression due to opioids in our Patient Safety Tips of the Week for July 13, 2010 “Postoperative Opioid-Induced Respiratory Depression” and September 21, 2010 “Dilaudid Dangers”.


And in our January 4, 2011 Patient Safety Tip of the Week “Safer Use of PCA” we noted that in 2006, in response to growing concerns about respiratory depression in patients due to opioid-induced respiratory depression, the APSF (Anesthesia Patient Safety Foundation) convened a workshop to address related issues (Weinger 2006). And in 2009 and 2010 the APSF again called for greater scrutiny of PCA (patient-controlled analgesia) in the postoperative period (Weinger 2009, Overdyk 2010). And ECRI  Institute in its Top 10 Health Technology Hazards for 2011 included oversedation during use of PCA infusion pumps as Number 7 on its list (see our January 2011 What’s New in the Patient Safety World column “ECRI’s Top 10 Health Technology Hazards for 2011”).


This month two more papers highlight the risks of death due to opioid-induced respiratory depression. A root cause analysis (Diamond 2011) on the sudden unexpected death of a young patient admitted with renal colic is particularly insightful. The patient likely died from respiratory depression related to opioid analgesics. Multiple communication issues occurred (faulty medication reconciliation, failure to buck the authority gradient, etc.) and there were issues concerning the understanding of the dosage of Dilaudid (akin to those raised in our September 21, 2010 Patient Safety Tip of the Week “Dilaudid Dangers”). The patient was also receiving other drugs that depress respiration. And, most important of all, the monitoring protocol was inadequate. The issues raised in this case are seen at hospitals across the country over and over.


In the second paper (Ramachandran 2011) the authors found 32 patients over a 6-year period who suffered life-threatening critical respiratory events in a population of postoperative patients receiving analgesic therapy at an academic medical center. These were adult patients who required rescue treatment with naloxone or endotracheal intubation or cardiopulmonary resuscitation. Four of the patients died. They found significant associations between the events and the following comorbidities: CHF, postoperative acute renal failure, obstructive sleep apnea, cardiac dysrhythmia, diabetes, CAD and hypertension. Interestingly, obesity and COPD were not more frequent in the group with complications. Over 40% received more than one type of opioid and Dilaudid was the primary opioid in three of the deaths. Deep sedation and nocturnal presentation were also notable in some cases, particularly those who died.


They found some very interesting findings regarding the timing of the events. Three of the four deaths occurred within the first 24 hours postoperatively (2 within 6 hours) and three of the four deaths occurred between midnight and 6 AM. Five of the 32 events occurred in the PACU and the rest occurred on general surgical floors. They note that some of the very early events may also reflect cumulative effects of the opioids plus residual effects of the anesthesia.


They also noted that many of the events occurred at relatively modest opioid dosages and when pain levels were still significant. That suggested that some might have an increased opioid sensitivity. Given the nocturnal occurrences and events at relatively modest opioid dosages, the authors speculated about the potential role of obstructive sleep apnea (OSA) in many patients. Two of the deaths occurred in patients with known OSA. The association with acute renal failure also suggested reduced opioid clearance or global organ dysfunction as contributing factors.


The study did not include details of the monitoring protocols used. You’ll recall in our February 22, 2011 Patient Safety Tip of the Week “Rethinking Alarms” we discussed a provocative article (Lynn 2011) on alarms and their failure to identify deteriorating patients early. The authors describe 3 patterns of unexpected in-hospital deaths and demonstrate the problems with threshold-based alarms (almost all currently used alarm systems use threshold-based principles) in detecting early deterioration. Indeed, they posit that threshold-based alarms themselves often cause us to miss signs of early deterioration.


One of the three patterns of deterioration they noted was the classic CO2 narcosis but they noted many of these cases are complicated by the third pattern, that typically seen in sleep apnea. The important point they made is that there may be a huge difference when the patient is awake and when he/she is asleep. In those with sleep apnea one sees repetitive reductions in airflow and oxygen saturation during sleep followed by arousals. The arousals rescue the patient but eventually the capacity or reserve of the patient to recover with arousals becomes impaired (often in response to narcotics or sedatives) and the patient may experience sudden death during sleep. The authors discuss the inability of currently used oximeters to recognize this pattern. They even imply that this pattern may give rise to oximeters alarming and being interpreted as “false” alarms attributed to motion artifact, etc. because when staff respond to the alarm the patient is now awake, breathing normally and has a normal oxygen saturation.


Warnings about this latter pattern become even more concerning given the significant percentage of patients being admitted who are at risk for sleep apnea (see our What’s New in the Patient Safety World columns for November 2010 “More on Preoperative Screening for Obstructive Sleep Apnea” and July 2010 “Obstructive Sleep Apnea in the General Inpatient Population”).


Lynn et al went on to discuss the flaws in current threshold-based alarm systems and the need for true “smart” alarms that integrate multiple physiological parameters and respond to patterns of changes in these. This article provides tremendous insight into why the concept of rapid response teams has proven disappointing to date. As we have mentioned in several of our own columns on rapid response teams, the problem is not with the response teams. Rather it is with our poor recognition of early clinical deterioration.


No one knows the actual incidence and prevalence of opioid-induced respiratory depression but it is likely much higher than one thinks. The ECRI paper notes that the true prevalence of respiratory depression in patients on PCA may be as high as 41%.


The ECRI recommendations are for monitoring not just vital signs but also mental status, pulse oximetry and capnography. The summary of a 2006 workshop on postoperative respiratory depression sponsored by APSF (Weinger 2006) noted most participants felt that the same monitoring should be applied to all patients, noting that even low-risk patients occasionally develop respiratory failure while receiving opioids by PCA or neuraxial techniques. They also note that avoiding even one case of patient harm from respiratory depression could justify the cost of monitoring all patients. Thus a policy of “zero tolerance” for harm due to postoperative opioid-induced respiratory depression should be the goal. They all noted inadequacies of current monitoring systems but recommend at least pulse oximetry and continuous respiratory monitoring on all patients on PCA. They stressed that oxygen should not be used unless there is a specific indication since oxygen therapy may significantly delay recognition of respiratory depression.


The problem of oxygen therapy complicating issues was also raised recently in another paper (Wijesinghe 2011). They looked at the effect of supplemental oxygen on hypercapnia in patients with the obesity-associated hypoventilation syndrome and found a significant and prompt increase in pCO2, similar to what is seen in COPD patients. They note that up to a third of morbidly obese patients may have this syndrome. They do note that the worsening of hypercapnia by oxygen was not universal in this population, speculating that their may be subgroups more vulnerable than others, a point stressed in the informative editorial accompanying that paper (Mokhlesi 2011).


We think it is particularly important in your use of opioids that you screen for those conditions which will increase the likelihood of respiratory depression. You may find helpful two tools we use when doing FMEA’s of the PCA pump process: the PCA Pump Audit Tool and the PCA Pump Criteria.





Prior Patient Safety Tips of the Week pertaining to opioid-induced respiratory depression:








Weinger MB. Dangers of Postoperative Opioids. APSF Workshop and White Paper Address Prevention of Postoperative Respiratory Complications. APSF Newsletter 2006; 21: 61-67  Winter 2006-2007



Weinger MB, Stoelting RK. Special Editorial. Dangers of Postoperative Opioids—Is There A Cure? APSF Newsletter 2009; 24(2): 25-26  Summer 2009



Overdyk FJ. Postoperative Opioids Need System-Wide Overhaul (Letter to the Editor). APSF Newsletter 2010; 24(4): 61, Winter 2009-2010



ECRI. ECRI Institute’s 2011 Top 10 Health Technology Hazards. Health Devices 2010; 39(11): 386-398



Diamond R. When pain management proves fatal. In-house errors lead to a patient's overdose. Today's Hospitalist May 2011



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(3): 207-213



Lynn LA, Curry JP. Patterns of unexpected in-hospital deaths: a root cause analysis. Patient Safety in Surgery 2011, 5:3 (11 February 2011)



Wijesinghe M, Williams M, Perrin K, Weatherall M, Beasley R. The Effect of Supplemental Oxygen on Hypercapnia in Subjects With Obesity-Associated Hypoventilation: A Randomized, Crossover, Clinical Study. Chest May 2011; 139(5) 1018-1024



Mokhlesi B, Tulaimat A, Parthasarathy S. Oxygen for Obesity Hypoventilation Syndrome: A Double-edged Sword?  Chest May 2011; 139(5): 975-977













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