Obtundation, Miosis, and Hypoventilation in a Young Man

What's The "Take Home"?
Pearls From Clinical Cases 

A 28-year-old man is brought to the hospital because of obtundation. He was fine in the morning, when his girlfriend went to work, but when she returned home at 5 o’clock, he was lying unresponsive on the couch and could not be aroused.

HISTORY

The patient has been receiving disability benefits for the past year because of chronic back pain apparently related to a work injury. He is taking a prescription analgesic for the pain. In the past he has had a variety of addictions and has been in rehabilitation “several times.”

PHYSICAL EXAMINATION

This stuporous young man is not arousable. Heart rate is 64 beats per minute; blood pressure, 105/60 mm Hg; and respiration rate, 6 breaths per minute and shallow. Miosis of the pupils is noted. Because breath sounds are decreased, the presence of rales or consolidation is difficult to ascertain. Bowel sounds are diminished. There is no warmth, swelling, or tenderness of the extremities.

LABORATORY RESULTS

Hemogram and basic blood chemistries are normal. An arterial blood gas sample reveals a PaO₂ of 90 mm Hg, a PaCO₂ of 46 mm Hg, and a pH of 7.37 on room air.

(Answer and discussion on next page)

Correct Answer: D

This patient presented with the typical clinical scenario of a person known to have an opioid addiction and in possession of potent oral opioid analgesics who exhibits obtundation/stupor, miosis and, most important, hypoventilation with a respiration rate of 6 or fewer breaths per minute.

EPIDEMIOLOGY OF OPIOID OVERDOSE

The epidemiology of opioid analgesic overdose has changed considerably in recent decades.¹ During the 1970s, such cases overwhelmingly resulted from the addictive use of intravenous opioids. Since 1995, however, intoxication related to prescribed potent oral formulations, such as controlled-release morphine sulfate, has become the more common cause. Statistics such as the 700% increase in opioid prescriptions between 1997 and 2007¹ suggest to the author and others² that the “pain as a fifth vital sign” initiative started around 1995 served as the unfortunate, though well intentioned at the time, genesis for this state of affairs. Therefore, physicians must be acutely aware of this situation when confronting a stuporous patient, and opioid overdose must be considered very early in the evaluation.

THERAPEUTIC MANEUVERS

In addition to non-specific therapy directed at any respiratory depression (eg, attention to the airway and varieties of assisted ventilation), naloxone remains the key therapy in suspected opioid overdose. Naloxone is a competitive antagonist to opioids at the mu opioid receptor. When given intravenously, naloxone has a very rapid (2-minute) onset of action, with a brief duration of only 20 to 30 minutes, much less than the half-life of most opioids; thus, continuous or repeated dosing is required.³

The following is true about the use of naloxone. Indeed, almost all findings encountered with the reversal of opioid dependence are possible and even probable, but none are life-threatening, which makes the reversal of respiratory depression, which is potentially fatal, the more over-riding goal. The problems of potential lacrimation, myalgia, emesis, and diarrhea are not contraindications, and choice B is an incorrect statement.

Of interest, naloxone does not reverse the problem of negative pressure pulmonary edema. A clue to this serious complication (which manifests in a majority of fatal opioid overdose cases⁴) is persistent hypoxemia even after administration of naloxone. Thus, naloxone does not address this noxious ventilatory/respiratory complication of opioid overdose, and choice C is not correct.

Finally, naloxone is generally effective in reversing essentially any opioid causative agent and has an overwhelmingly positive risk-benefit ratio in suspected cases of drug-related respiratory depression. Therefore, it should not be withheld pending the results of routine drug screens available in most emergency departments. Choice A is thus not appropriate.

Choice D is correct because there is a need to determine, as practicable, whether or not other agents have been ingested to toxic excess, such acetaminophen which will manifest as high transaminase concentrations in a routine early blood sample, or can be detected even more accurately by obtaining specific levels. Multiple ingestions are quite common in overdose cases. In addition, a collateral complication of opioid intoxication is obtundation to the point of dependency-related compartment syndromes (due to lying on an arm, bent leg, etc), a clue to which will be elevated creatine kinase. This can be managed with appropriate fluid regimens. Thus, early use of easy and relatively routine additional blood analysis can result in effective therapeutic maneuvers in addition to naloxone opioid reversal itself.

OUTCOME OF THIS CASE

Naloxone 3 mg was immediately administered with prompt awakening and improvement in ventilation and hypoxemia. Once the patient was awake, a clear history of excessive controlled-release morphine sulfate ingestion was obtained. Naloxone was continuously infused over an 8-hour period. A chest film and minor residual hypoxemia revealed mild pulmonary edema, which resolved by the next morning. Creatine kinase and transaminase levels did not materially rise either on admission or pre-discharge testing the next morning. 

REFERENCES:

1.Boyer EW. Management of opioid analgesic overdose. N Engl J Med. 2012;367:146-155.

2.Okie S. A flood of opioids, a rising tide of deaths. N Engl J Med. 2010;363:1981-1983.

3.Evans JM, Hogg MI, Rosen M. Degree and duration of reversal by naloxone of effects of morphine in conscious patients. BMJ. 1974;2:589-591.

4.Sporer KA, Dorn E. Heroin-related noncardiogenic pulmonary edema: a case series. Chest. 2001;120:1628-1632.