Identifica tion and Management of Cardiac -Adrenal-Pain Syndrome

Severe, chronic, under-treated pain may produce cardiac and adrenal complications, that in some pain patients, can lead to premature death.
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Severe pain is well-known to stimulate the cardiac and adrenal systems.1-7 Despite this knowledge, there are few reported systematic investigations of these complications in clinical patients. More importantly, clinical treatment of pain’s complications on the cardiac and adrenal systems has not heretofore been practically addressed.

Those chronic pain patients who demonstrate physiologic complications involving the heart and adrenal glands are obviously those who have a most serious pain problem and who must be managed with the most aggressive measures.6,7 Reported here are two systematic investigations of some cardiac and adrenal complications in severe, chronic pain patients. The results of these efforts clearly show that some patients demonstrate cardiac and adrenal complications that can be easily diagnosed in an outpatient clinical setting and which can usually be controlled or ameliorated by aggressive pain treatment. The most obvious and easily detectable cardiac complications are tachycardia and hypertension. Severe pain causes the adrenal glands to secrete abnormal levels of catecholamines (e.g., adrenalin) and glucocorticoids (e.g., cortisol). Pain’s impact on the adrenal gland is biphasic.2 Severe pain initially causes an outpouring of catecholamines and glucocorticoids in an effort to neutralize pain’s adverse affects (see Figure 1), but the adrenal gland may later exhaust if pain is severe and unremitting.2 At this time, serum testing may demonstrate severe hormonal deficiencies.4 The tachycardia and hypertension observed in severe chronic pain patients is at least partially the result of excess adrenal hormone production, but central nervous system over-stimulation produced by severe pain also contributes to tachycardia and hypertension.6,7 Over-stimulation of the pituitary-adrenal axis and other adrenergic centers in the brain appear to act concordantly. It is pain’s over-stimulation of the nervous system that is the root cause of most cardiac and adrenal complications, and they can be identified by simple clinical screens. Once identified, treatment can be partially guided by on-going monitoring of these complications.

Figure 1. Schematic of the effects of excess pain on the hypothalmus-pituitary-adrenal axis with some of the serious cardiac-adrenal complications shown.

Background

Beginning in the 1960’s, investigators began to report cardiac and adrenal abnormalities in clinical pain patients as well as in experimental studies. Initially these abnormalities were considered biologic tracers or markers rather than serious complications of pain. Shenkin, in 1964, first observed that chronic pain changed the diurnal patterns of plasma cortisol levels.1 Since this report, other observers have recognized cortisol abnormalities in acute and chronic pain patients, including post-operative patients.1-3 Reduced adrenal reserve has been documented in severe, chronic, intractable pain patients.2 Elevated blood pressure and pulse rates have been observed both in clinical patients with acute and chronic pain and under experimental conditions.3,6,7

In 1999, Richard Chapman wrote a seminal article entitled “Suffering: The Contributions of Persistent Pain.”8 Chapman hypothesized that much of the suffering and agony had to be, at least in part, the over-stimulation of the hypothalamus-pituitary-adrenal axis, since severe pain is basically a severe stressor. Indeed Liebeskind wrote that “Pain can kill” and others have also described the immense suffering and medical necessity to treat severe pain.6,9 The motivation for the investigations reported here was to document whether the stress of severe, chronic pain causes a clinical cardiac-adrenal-pain syndrome which can be identified in clinical patients and, if so, whether pain treatment can ameliorate these complications.

Identification of a Cardiac-Adrenal-Pain Syndrome

To initially determine if there is an easily detectable cardiac-adrenal-pain syndrome, 91 consecutive, severe chronic pain patients who were admitted to the author’s outpatient intractable pain treatment clinic in California were evaluated. At the time of referral, they were screened for the following complications:

  1. Blood pressure above 130/90mmHg
  2. Pulse rate over 84 per minute
  3. Early morning serum cortisol above 20 or below 5ug/dl
  4. Erythrocyte sedimentation rate (ESR) above 20mm per hour

ESR was included as a screening tool because excess adrenal hormone secretion and stress are known to cause a variety of immune changes.10,11

All subjects were adults between the ages of 30 and 62 years. Females and males constituted, respectively, 54% and 46% of the group. Their pain duration ranged in length from 1 to 45 years. To be eligible for this study, their pain had to be described as severe, constant, and interfered with sleep, eating, dressing, or other activities of daily living. All patients were referred to the clinic after failing to achieve pain control by a plethora of standard measures including psychotherapy, physical therapy, paraspinal corticoid injections, non-opioid medications, and standard dosages of weak opioids. All patients were taking a weak opioid in the form of hydrocodone, tramadol, propoxyphene, or codeine at the time of referral. Without opioid medication, patients claimed to be incapacitated and confined to home or bed.

Cardiac and/or adrenal complications were readily apparent (see Table 1). Only 7 (7.7%) of patients failed to demonstrate at least one cardiac or adrenal abnormality. The majority demonstrated elevated blood pressure (60, 65.9%) or elevated pulse rate (46, 50.5%). Seventeen (18.7%) had pulse rates over 100 per minute (see Table 1). Forty-seven (47.3%) had either elevated or reduced serum cortisol and 33% showed an elevated sedimentation rate. There was considerable demonstration of multiple abnormalities in a single patient. Fifty-nine (64.5%) had two or more abnormal screening tests. Twenty-five (27.4%) had three abnormal screens and four (4%) demonstrated the presence of all four screens. Results in this initial study clearly indicated that severe, chronic pain that was constant and debilitating produced easily detectable cardiovascular and adrenal complications.

Will Pain Treatment Ameliorate Cardiac-Adrenal

Complications?

Since the pilot screening study showed that cardiac-adrenal complications could be easily detected, a second study was done to determine if pain treatment could eliminate or ameliorate these complications. The working premise was that improvement in cardiac and adrenal complications from adequate pain treatment would provide evidence that severe, chronic pain itself, and not some other condition, was producing the observed cardiac-adrenal abnormalities.

First published on: September 1, 2006