Every year, from 350,000 to 750,000 in-hospital cardiopulmonary arrests (IHCAs) occur in the United States. About 80% of the victims don’t survive to discharge; among those who do, some suffer permanent anoxic brain injury. Patient outcomes haven’t improved measurably in 40 years.
Studies show roughly half of patients with IHCAs had been receiving opioids. Opioid-induced respiratory depression (OIRD) has an insidious progression. Hard to diagnose, it’s likely to lead to death or anoxic brain injury unless detected promptly. Outcomes are worse when IHCA occurs at night or on the weekend, when staffing levels and patient interaction are lowest.
Two leading factors influence IHCA outcomes—whether the event was witnessed and how soon cardiopulmonary resuscitation (CPR) begins. In intensive care units (ICUs) and emergency departments (EDs), IHCAs typically are witnessed, and responders and equipment are available immediately to start CPR. But on med-surg units, patients’ vital signs may be taken only every 4 hours and rapid response teams (RRTs) have to be summoned from remote locations. Although estimates of OIRD incidence among postsurgical med-surg patients range from 0.5% to 2%, a study using continuous pulse oximetry and end-tidal carbon dioxide (EtCo2) monitoring suggests OIRD is much more common among this population.
The truth about IHCA
Many healthcare providers assume IHCA correlates with chronic advanced disease states and advanced age. Yet IHCA victims have a low prearrest morbidity score—a measure of the degree of sickness. What’s more, their average age is only 57 and their median hospital stay is
IHCA resuscitation studies have shed light on the common causes and time course of the pathophysiologic deterioration that precedes an IHCA. A detailed review of 139 in-hospital deaths found IHCAs were potentially avoidable in 62% of cases, and clinical signs of deterioration went unattended in 48% of cases. Also, med-surg patients were five times more likely to suffer avoidable IHCAs than ICU patients and accounted for nearly two-thirds of hospital deaths.
Why respiratory monitoring is crucial
Historically, hemodynamic monitoring (blood pressure, heart rate, and heart rhythm) has taken center stage in bedside patient assessment. To reduce the risk of unexpected and unrecognized cardiac arrhythmias, hospitals have established cardiac telemetry units for continuous remote monitoring of patients at risk for rhythm disturbances.
Yet the most common events preceding IHCAs are respiratory—not arrhythmias or hemodynamic disturbances. Typically, the earliest warning signs of physiologic instability reflect respiratory decompensation—tachypnea, bradypnea, hypoxia, hypercarbia, and mental status changes. Monitoring of respiratory function and level of consciousness (LOC) is especially crucial in preventing adverse events in med-surg patients receiving opioids and sedatives. Unfortunately, few hospitals have the capacity to monitor these indices remotely and continuously, except in ICU or step-down settings.
Evaluating for OIRD warning signs
Many clinicians mistakenly focus on the respiratory rate (RR) when assessing patients for OIRD. But evaluating LOC is more likely to uncover warning signs of OIRD.
Fiction: A slow RR (less than 8 breaths per minute [bpm], or bradypnea) is the most important and sensitive vital-sign warning of OIRD.
Quote: “The patient can’t possibly have had a respiratory arrest. In the 2 hours before the code, his charted respiratory rates were 16 and 12.” (Note: This quote and the other quotes in this article are actual clinician statements.)
Fact: Although opioids commonly cause bradypnea, absence of bradypnea doesn’t rule out respiratory depression. Reduced LOC, not a slow RR, is the clinical finding with the best chance of not missing OIRD detection.
The Pasero Opioid-Induced Sedation Scale (POSS) was designed specifically to assess opioid-induced mental status changes. A survey-based study found POSS demonstrated adequate measures of reliability and validity in measuring sedation during opioid administration for pain management. It also found POSS has clinical significance in determining the accuracy of clinical assessments and subsequent actions for patients experiencing advancing sedation during opioid analgesia. But no sedation scale is specific for opioid-induced sedation, so clinicians should consider other diagnoses once opioid overdose is ruled out.
Pitfalls in measuring and interpreting RR and LOC
Not only is RR a poor measure of overall respiratory function, but manual RR measurement is the most difficult bedside vital-sign measurement to take and in many cases is inaccurate. An accurate RR measurement requires a prolonged sampling period and careful attention to detail, including observation of breathing depth and pauses. A respiratory hallmark in patients receiving opioids is irregular breathing, not just slow breathing.
Thus, measuring RR over 30 seconds may yield a false-low or false-high result. Triggers for summoning the RRT commonly are set at an absolute threshold of 8 bpm or less for bradypnea and 90% or less for peripheral oxygen saturation (Spo2). Consequently, clinicians may misinterpret the patient’s respiratory status and take inappropriate measures, as described in the clinical examples that follow.
Clinical example A
Although the patient’s RR is measured at 8 bpm, he’s taking markedly deep breaths. He rates his pain as 2 on a scale of 0 to 10, and is awake and oriented to person, place, and time. The nurse lengthens the lockout interval on the patient-controlled analgesia (PCA) pump to prevent further RR slowing.
Explanation: A slow RR is a normal physiologic response to opioids. An RR of 8 bpm may not warrant intervention if the patient is awake, appropriate, and comfortable. In this case, backing off the PCA opioid regimen is inappropriate, as it may exacerbate the patient’s pain. And calling the RRT based on a breach of the RR threshold of 8 bpm would constitute a false alarm. Instead, the nurse should identify and grade changes in the patient’s sedation level and respiratory quality, including changes in respiratory pattern and depth and noisy breathing. (See Are RRT triggers appropriate? by clicking the PDF icon above.)
Clinical example B
The patient is breathing at 12 to 15 bpm but is lethargic and complains of 8/10 pain when aroused. A spot Spo2 value of 95% is measured with a bedside oximeter.
Explanation: This scenario was replicated multiple times in a study measuring continuous oximetry and capnography in patients receiving PCA. The study found patients had significant clinical respiratory depression with end-tidal capnography values above 55 mm Hg. Their sedation stemmed from hypercarbia, yet their Spo2 values remained normal—even though not all of the patients were receiving supplemental oxygen by nasal cannula. In these cases, the RRT respiratory triggers of an RR of 8 bpm or lower and Spo2 below 90% were falsely negative, and the patients could have suffered respiratory arrest. (See Stay alert for false-negatives by clicking the PDF icon above.)
Clincial example C
At 4 a.m., your patient is curled up under the bedcovers and snoring lightly as you perform a routine bedside assessment. When you awaken her to evaluate her pain and sedation levels, you find her slow to arouse, disoriented, and speaking incoherently. She falls asleep during your assessment; you measure an RR of 10 bpm and note that her PCA button was last pressed at 2 a.m.
Explanation: This scenario highlights the difficulty of patient assessment during the early morning hours. The patient’s disorientation may stem from being awakened from slow-wave or rapid-eye-movement (REM) sleep—or she might be hypercarbic and have significant respiratory depression. The two conditions can’t be differentiated without more extensive investigation, which may be impractical and is often avoided at this hour. Yet, most catastrophic outcomes from unrecognized respiratory depression occur in the early morning.
Understanding the variable effects of opioids
Various factors influence the safety with which opioids can be given postoperatively. Because the effects of a given opioid dosage may vary greatly among patients, dosages must be individualized. (See Factors influencing opioid effects by clicking the PDF icon above.)
Fiction: A standard dosage of an opioid is always safe.
Quote: “This patient can’t have had a respiratory arrest because he was getting a standard morphine dosage by PCA.”
Fact: There’s no standard opioid dosage that guarantees a patient will avoid respiratory depression; there’s only a starting dosage. The only way to ensure a safe and effective opioid-based analgesic regimen is to carefully and frequently titrate the starting-dose regimen (including PCA) to the patient’s pain and sedation scores and to assess vital signs frequently.
Analgesic variability results from differences in both pharmacokinetics (relationship between drug dose and drug blood level) and pharmacodynamics (relationship between drug blood level and drug effect) among patients. Examples of pharmacokinetic and pharmacodynamic factors include the following:
- Gender: Morphine has a slower analgesic onset (pharmacokinetic factor) in women than in men, but is more potent in women (pharmacodynamic factor).
- Genetics: The mu-opioid receptor (MOR) has genetic variability (polymorphism), which means patients differ in morphine sensitivity depending on their genetic makeup.
- Drug interactions: Residual intraoperative anesthetics, sedatives, and opioids act synergistically or additively with opioids’ sedative and respiratory depressant effects postoperatively.
- Comorbidities: Sleep apnea and certain other conditions predispose patients to airway collapse; also, liver and kidney failure affect metabolism and excretion of opioids and their active metabolites.
- Sleep and diurnal rhythms: Transient airway collapse is the hallmark of obstructive sleep apnea (OSA). Yet anesthetics and sedatives produce similar effects in patients without OSA. Thus, all postoperative patients (who typically experience sleep deprivation and REM-sleep rebound) are at risk for unpredictable episodes of airway obstruction, especially at night.
- Pain level: Pain stimulates the respiratory centers and promotes airway patency. Fluctuations in pain levels due to intermittent opioid dosing or regional anesthesia cause fluctuations in respiratory depression.
Postoperative management of patients with chronic pain
The population of surgical patients taking long-term opioids is rising rapidly. Twelve million people in the United States took opioids for nonmedical reasons in 2007. Many more took them for chronic pain syndromes.
Postoperative patients on long-term opioid therapy need the same meticulous monitoring for drug side effects as opioid-naïve patients. Respiratory depression remains a prominent cause of death in opioid-addicted individuals and in patients receiving intrathecal opioids for chronic pain syndromes.
Postoperative patients with chronic pain are unlikely to experience significant respiratory depression after receiving starting opioid dosages typically given to opioid-naïve patients. But these patients rarely receive those opioid dosages, because their opioid tolerance and opioid-induced hyperalgesia mean that providers must rapidly escalate therapy to higher dosages and use multimodal opioid analgesics (such as I.V. or transdermal administration) to meet pain treatment guidelines. At these higher dosages, chronic-pain patients are susceptible to respiratory depression.
Fiction: Patients on long-term opioid therapy are less likely than opioid-naïve patients to suffer respiratory depression from postoperative opioids.
Quote: “Ms. Caldwell took a lot of pain pills at home. There’s no way she can go into respiratory arrest while using PCA.”
Fact: Patients on long-term opioid therapy have higher opioid requirements for adequate pain relief. At these higher dosages, they’re just as susceptible to respiratory depression as opioid-naïve patients are at lower dosages. Also, patients on long-term opioids have baseline respiratory abnormalities—specifically, increased periods of central apnea and ataxic breathing—which opioids and sedatives may exacerbate postoperatively.
Fiction: A patient with a high pain level can’t experience respiratory depression.
Fact: Although pain stimulates respiratory centers and promotes airway patency, recent studies suggest respiratory depression can occur without adequate analgesia; high plasma morphine levels causing respiratory depression don’t correlate with low pain scores. Further clinical and laboratory assessment may be needed to determine appropriate interventions in this difficult scenario.
Fiction: Some opioids don’t cause respiratory depression.
Fact: Opioids’ analgesic and respiratory depressant effects are inalterably linked at a common locus—the MOR. Extensive research on alternative opioid ligands and receptors has failed to find an analgesic opioid that doesn’t depress respiratory drive. The most effective way to prevent respiratory depression is to use opioid-sparing analgesic agents in combination with opioids to reduce the required opioid dosage. Examples of these agents include local anesthetics, nonsteroidal drugs, cyclooxy-genase-2 inhibitors, ketamine, gabapentin, partial opioid agonist-antagonists, and even chili peppers. Other opioid-sparing modalities include regional postoperative pain therapies, transcutaneous nerve stimulation, and transcranial magnetic stimulation.
What the future may hold
Respiratory decompensation on med-surg units is likely to become more common as the demographic of surgical patients shifts towards older and more overweight individuals. What’s more, intermittent airway obstruction and central apnea are common in patients who’ve received general anesthesia—and will grow more prevalent with the expanding population of patients who have sleep-disordered breathing and OSA.
Most clinicians acknowledge that unrecognized adverse respiratory events in patients receiving opioids stem largely from the intermittent nature of bedside monitoring. Various strategies are being used in response to such deficiencies. The most recent guidelines from the
definitive nursing text on bedside monitoring for patients on opioids recommend a much shorter interval between bedside vital-sign assessments, despite the extra burden this imposes on staff. Some healthcare systems have implemented continuous respiratory monitoring of Spo2, EtCo2, or both on med-surg units (with or without telemetry)—with satisfactory results. A recent study suggests centrally monitored continuous oximetry with wireless provider notification may reduce RRT calls and transfers to the ICU.
However, according to the Consensus Conference on Medical Emergency Teams, recommending this technology would be premature because of the high false-positive rate and associated costs and workflow disruption of continuous respiratory monitoring equipment. Promising new developments in monitoring and alarm technology are improving specificity (resulting in fewer false-positives) without compromising sensitivity by increasing false-negatives. Monitors will include smaller body-borne wireless sensors that yield higher-resolution data with better motion detection and artifact rejection. Monitors will no longer use simple arbitrary thresholds of a single parameter, such as heart rate or Spo2, to trigger an alarm. Instead, they’ll fuse multiple vital signs into heuristic
algorithms that interpret the whole clinical picture, much like a clinician would do at the bedside.
OIRD and IHCA result in more serious adverse events for med-surg patients than for patients in ICUs and EDs—monitored settings where arrests are likely to be witnessed and therapeutic interventions can begin at once. Early recognition of respiratory compromise and timely intervention through improved monitoring, staffing levels, and resources are urgently needed to improve the tragic and preventable illnesses and deaths from OIRDs and IHCAs among med-surg patients.
Chan PS, Khalid A, Longmore LS, Berg RA, Kosiborod M, Spertus JA. Hospital-wide code rates and mortality before and after implementation of a rapid response team. JAMA. 2008 Dec 3;300(21):2506-13.
Combes X, Cerf C, Bouleau D, et al. The effects of residual pain on oxygenation and breathing pattern during morphine analgesia. Anesth Analg. 2000 Jan;90(1);156-60.
Dahan A, Romberg R, Teppema L, et al. Simultaneous measurement and integrated analysis of analgesia and respiration after an intravenous morphine infusion. Anesthesiology. 2004 Nov;101(5):1201-9.
DeVita MA, Bellomo R, Hillman K, et al. Findings of the first consensus conference on medical emergency teams. Crit Care Med. 2006 Sep;34(9):2463-78.
Fecho K, Jackson F, Smith F, Overdyk FJ. In-hospital resuscitation: opioids and other factors influencing survival. Ther Clin Risk Manag. 2009;5:961-8.
Hutchison R. Rodriquez L. Capnography and respiratory depression. Am J Nurs. 2008 Feb;108(2):35-9.
Mogri M, Desai H, Webster L, et al. Hypoxemia in patients on chronic opiate therapy with and without sleep apnea. Sleep Breath. 2009 Mar;13(1):49-57.
Overdyk FJ, Carter R, Maddox RR. Continuous oximetry/capnometry monitoring reveals frequent desaturation and bradypnea during patient-controlled analgesia. Anesth Analg. 2007 Aug;105(2):412-8.
Pasero C. Assessment of sedation during opioid administration for pain management.
PeriAnesthesia Nurs. 2009;24(3):186-90.
Pattinson KT. Opioids and the control of respiration. Br J Anaesth. 2008 Jun;100(6):747-58.
Peberdy MA, Ornato JP, Larkin GL, et al; National Registry of Cardiopulmonary Resuscitation Investigators. Survival from in-hospital cardiac arrest during nights and weekends. JAMA. 2008 Feb 20;299(7):785-92.
Sandroni C, Nolan J, C¬¬avallaro F, Antonelli M. In-hospital cardiac arrest: incidence, prognosis and possible measures to improve survival. Intensive Care Med. 2007 Feb;33(2):237-45.
Sarton E, Olofsen E, Romberg R, et al. Sex differences in morphine analgesia: an experimental study in healthy volunteers. Anesthesiology. 2000 Nov;93(5):1245-54.
Taenzer AH, Pyke JB, McGrath SP, et al. Impact of pulse oximetry surveillance on rescue events and intensive care unit transfers: a before-and-after concurrence study. Anesthesiology. 2010 Feb;112(2):282-7.
Whipple JK, Quebbeman EJ, Lewis KS, Gottlieb MS, Ausman RK. Difficulties in diagnosing narcotic overdoses in hospitalized patients. Ann Pharmacother. 1994 Apr;28(4):446-50.
Yassen A, Dahan A, Overdyk FJ, et al. Verbal pain scores are not linearly related to morphine plasma levels during PCA. Anesthesiology. 2007;107:A1247.
Frank J. Overdyk is an adjunct professor of anesthesiology and perioperative medicine at the Medical University of South Carolina in Charleston. Jesse J. Guerra is a board-certified pain-management nurse and a clinical manager at CareFusion in San Diego, California.