Pain Medicine

Ventilatory depression, a significant risk associated with the use of opioids, may occur in up to 17% of patients with potentially fatal outcomes. Agents that modulate neuronal pathways responsible for respiratory drive while maintaining opioid analgesia may provide significant clinical benefit. AMPA receptors are responsible for respiratory rhythmogenesis maintenance and the ampakine CX717 counteracted opioid-induced ventilator depression in preclinical studies.

A double-blind, placebo-controlled, crossover study assessed the effects of CX717 pretreatment on opioid-induced ventilatory depression in healthy volunteers (N = 16). Patients received a single oral dose of either 1,500 mg CX717 or placebo. Volunteers also received a 2-h intravenous infusion of alfentanil (target concentration, 100 ng/ml) for 100 min and 1.6 mg naloxone for 160 min after CX717 administration, respectively.

After CX717, alfentanil decreased the respiratory frequency by only 2.9 ± 33.4% compared with 25.6 ± 27.9% during placebo coadministration (P < 0.01). Blood oxygenation and the ventilatory response to hypercapnic challenge also showed significantly smaller decreases with CX717 than with placebo. In contrast, CX717 did not affect alfentanil-induced analgesia in either electrical or heat-based experimental models of pain. Both ventilatory depression and analgesia were reversed with 1.6 mg of naloxone. CX717 was well tolerated, and no volunteers required interventions for side effects. However, CX717 did produce a significant increase in tiredness during combination treatment with alfentanil (P = 0.03).

Opioid-induced respiratory depression is common in the perioperative period. To date, only opioid receptor blockade can be used to reverse opioid-induced respiratory depression; however, analgesia is compromised by opioid-receptor antagonism. This study shows a novel mechanism for reversal of respiratory depression by opioids without affecting analgesia.

There are documented reports of selective outcome reporting in published reports of randomized clinical trials. These may include modifications to primary endpoints after statistical testing has been completed and may constitute bias reporting.

To examine the reporting practices for trials of gabapentin funded by Pfizer and Parke-Davis for off-label indications (prophylaxis against migraine and treatment of bipolar disorders, neuropathic pain, and nociceptive pain), 20 internal company documents were matched and compared with 12 published reports. Many of the source documents were available as a result of recent litigation:

Of the 28 primary outcomes described in the published reports, 12 were newly introduced. Trials that presented findings that were not significant (P ≥ 0.05) for the protocol-defined primary outcome in the internal documents either were not reported in full or were reported with a changed primary outcome.

For these industry-sponsored clinical trials for gabapentin that included trials of neuropathic pain, modification of outcome reporting was noted in some of these trials. This report supports registration of clinical trials to ensure that the outcome of the research is fully understood.

Nonbattle-related injuries are the leading basis for soldier attrition; specifically, spine pain and other musculoskeletal conditions are associated with the lowest return-to-unit rate among service members medically evacuated out of Operations Iraqi and Enduring Freedom. Similar to the civilian sector, nonantomical factors (e.g. , psychopathalogic and psychosocial stressors) are major determinants of disability. This prospective study was conducted to identify which variables are associated with return to unit in soldiers with back pain.

Data were prospectively collected at the Deployed Warrior Medical Management Center in Germany on 1,410 consecutive soldiers between 2004 and 2007. These soldiers were all medically evacuated out of combat for a primary diagnosis related to back pain.

Of the 1,410 soldiers, 92% were men, 54% had a history of low-back pain, and 28% had a coexisting psychiatric disease. The mechanism of injury was unknown in 66% of cases, attributed to lifting objects (18%) or from falls (11%). Only 5% were sustained during combat.

The overall return-to-unit rate was only 13%. Women were 57% more likely to return to duty after injury as were patients with a history of lower back pain (50%). Additional factors associated with a positive outcome included deployment to Afghanistan and being an officer. Trends toward not returning to duty were found for navy and marine service members, coexisting psychiatric morbidity, and not being seen in a pain clinic.

Return-to-unit rate of soldiers with back pain was low. Future studies will determine whether treatment can improve the low return-to-unit rate of soldiers deployed for combat.