Sudden, Unexpected Death in Chronic Pain Patients

Sudden, Unexpected Death in Chronic Pain Patients – By Forest Tennant, MD, DrPH – Sep 2012

Sudden, unexpected death may occur in a severe, chronic pain patient, and the terminal event may be unrelated to medical therapeutics. Fortunately, sudden death is not as commonly observed in pain patients as in past years most likely due to better access to at least some treatment. Sudden death still occurs, however, and practitioners need to know how to spot an “at-risk” patient.

For observers, pain is merely a “harmless nuisance”. For those suffering from it, it’s a”physiologic calamity”.

It all depends on who is observing pain and who is experiencing pain.

Unexpected, sudden death due to severe pain is poorly appreciated, since many observers still view severe pain as a harmless nuisance rather than a potential physiologic calamity.

Modern medicine’s aggressive toxicology and forensic procedures after death have contributed to the poor understanding of pain’s death threat.

In some cases, a pain patient that was being treated appropriately with an opioid or other agent with overdose or abuse potential has suddenly and unexpectedly died.

This article is partially intended to call attention to the fact that the mere finding of abusable drugs at autopsy doesn’t necessarily mean that the drugs caused the death.

Additionally, opioid blood levels assessed at autopsy of a patient who died suddenly are all too often wrongfully considered accidental overdoses because the pathologist is unaware that:

chronic pain patients on a stable dose of opioids can be fully functional with serum levels of their prescribed opioids that far exceed lethal levels in opioid-naïve patients.

A Brief Anecdotal History

In making our rounds one day to the county’s nursing home, I heard a farmer’s wife declare, “pain killed my mother last night.” Since then, I’ve repeatedly heard that pain killed a loved one. Folklore frequently mentions that people die “from,” as well as “in” pain. There is, however, little written detail of these events.

In the early years of my pain practice, which I began in 1975, I had several patients die suddenly and unexpectedly. This rarely happens to me today as I’ve learned to “expect the unexpected” and to identify which patients are at high risk of sudden death.

Setting and Cause

Unexpected deaths in chronic pain patients usually occur at home.

Death often occurs during sleep or when the patient gets up to go to the toilet. In some cases, the family reports the patient spent an extraordinary amount of time on the toilet just prior to collapse and death

Coronary spasm and/or cardiac arrhythmia leading to cardiac arrest or asystole is the apparent cause of death in the majority of these cases, since no consistent gross pathology has been found at autopsy.

Instant cardiac arrest appears to account for sudden collapse or death during sleep.

Two Mechanisms of Cardiac Death

Severe pain is a horrific stress.

Severe pain flares, acute or chronic, cause the hypothalamic-pituitary-adrenal axis to produce glucocorticoids (cortisol, pregnenolone) and catecholamines (adrenalin and noradrenalin) in an effort to biologically contain the stress

Catecholamines have a direct, potent stimulation effect on the cardiovascular system and severe tachycardia and hypertension result.

In addition to adrenal catecholamine release, pain flares cause overactivity of the autonomic, sympathetic nervous system, which add additional stimulation to catecholamine-induced tachycardia and hypertension.

The combined physiologic effects of excessive catecholamine release and autonomic, sympathetic discharge may put such strain on the heart to cause coronary spasm, cardiac arrhythmia, and sudden death.

Even if a patient doesn’t suffer extreme pain flares, chronic pain that goes on for weeks and months and years and even decades causes constant activation of the body’s stress systems. The slow erosion of the body’s defenses and constantly overactive nervous system can also lead to a shortened lifespan.

Identification of the At-risk Patient

An active, ambulatory pain patient who has mild to moderate, intermittent pain is not at high risk for sudden death.

I’m grateful for my intermittent pain because it gives me little breaks here and there so I can rest and recuperate from pain’s assault on my nervous system.

However, after decades of going through daily pain of some kind, I know my nerves are “frazzled”, my resistance to depression and anxiety is lowered, and my quality of life is slipping away from me.

The patient at high risk for sudden death is a severe pain patient who is functionally impaired and has to take a variety of treatment agents, including opioids and neuropathic drugs, to control pain.

Excess sympathetic discharge signs that can be discerned at the bedside, emergency room, or accident site include mydriasis, diaphoresis, hyperthermia, tachycardia, hypertension, and hyperreflexia

The chronic pain patient who is at high risk for sudden death can usually be spotted at a clinical visit (Table 1).

Patient and family will give a history of functional impairment. The most typical history will be one in which the patient will have constant, daily pain intermixed with severe flares, which cause a bed or couch-bound state. Even though medication dosages may be high, they may not be effective enough to prevent pain flares and sudden death.

Cortisol, pregnenolone, or corticotropin (adrenocorticotropic hormone) serum levels may be subnormal indicating that the immune and healing systems are impaired, leaving the patient subject to infections and interference with opioid effectiveness.

Risk of Sepsis

Although not well documented, acute sepsis and sudden death probably occur in some severe, chronic pain patients. The mechanism is probably initiated by subnormal serum levels of cortisol or other hormones due to adrenal depletion.

Although documentation of this pathologic event is scant, practitioners should be aware that extremely low serum levels of adrenal hormones are known to be associated with a compromised immune system and sepsis.

Death Following Sudden Opioid Cessation

There is the misguided notion among some addiction and mental health practitioners that withdrawal from opioids is an innocuous procedure that is risk free. 

This is generally true unless the patient who is dependent upon opioids has severe underlying pain and is taking opioids solely for pain control. In some patients, opioids may mask underlying pain so well that a practitioner may not even believe that pain recrudescence is a possibility once opioids are stopped.

If opioids in a severe pain patient are precipitously stopped, the masked pain may flare causing severe autonomic, sympathetic discharge and overstimulation of the adrenals to produce excess catecholamines with subsequent cardiac arrhythmia and arrest

Value of Opioid Serum Levels

Patients who have severe chronic pain, take opioids, and demonstrate some high-risk signs and symptoms for sudden death as described above should have opioid blood levels done. Why? Legal protection.

If a severe chronic pain patient who takes opioids suddenly dies, the practitioner may be accused of overprescribing and causing an overdose death unless he/she has pre-death opioid blood levels on the patient’s chart.

Keep in mind that there will be no gross cardiac pathology at autopsy if the patient suddenly dies of a cardiac arrhythmia or arrest. And, the coroner will likely call the death a drug overdose and blame the prescribing physician

Here are two illustrative cases.

Summary

Although sudden, unexpected death in chronic pain patients appears to be declining in incidence due to greater access to treatment, practitioners need to be aware that sudden, unexpected death may occur independent of opioid administration.

The precise mechanism of death is cardiac arrest or asystole due to coronary spasm, arrhythmia, and/or electrolyte imbalance.

Severe chronic pain produces excess sympathetic discharge through the autonomic nervous system and overstimulation of the hypothalamic-pituitary-adrenal axis, which causes great output of adrenal catecholamines.

The chronic pain patient who is at highest risk for sudden death is the patient whose uncontrolled pain and pain flares are so great as to cause a high degree of functional disability.

Those pain patients who are ambulatory and active are not at high risk for sudden death

This is exactly why my doctor prescribes me opioids: to remain ambulatory and active.

Pain management practice in the past used to encourage patients to take their opioid pain medication before physical therapy so that they would get the benefit of exercise.

The attainment of opioid blood levels during treatment of patients who are at high risk for sudden death are advised as a medical-legal protection should opioids be present in blood after death.

Patients who are identified as high risk should be monitored by regular clinic visits, and efforts should be done to control excess sympathetic discharge and adrenal deficiencies.