Opioid prescriptions for chronic pain and overdose. Ann Int Med 2010; 152:85–92
Because awareness of chronic noncancer pain as an important patient problem is increasing, so is opioid prescribing. This is associated with an increased risk of overdose and opioid overdose fatalities. However, the proportion of risks attributed to patients receiving medically prescribed long-term opioid therapy and the effect of dose are unknown.
The Consortium to Study Opioid Risks and Trends study examined the medical records over an 8-yr period to estimate overall overdose rates among patients receiving long-term opioid therapy for noncancer pain from clinicians and to examine the effect of opioid dose on risk. Data from the Group Health Cooperative in Washington were collected from the records of adult patients who documented the initiation of long-term opioid prescribing for chronic noncancer pain.
The mean age of patients (n = 9,940) was 54 yr, mean follow-up was 42.1 person months, back pain (37.9%) and extremity pain (30.3%) were the most common pain diagnoses, and the mean dose of opioids was 13.3 mg/day of morphine equivalents. The most common opioids prescribed were hydrocodone (46.3%) and oxycodone (24.5%). There were 51 opioid-related overdoses and 6 deaths. Compared with patients receiving 1 to 20 mg/day of morphine equivalent opioids (0.2% annual overdose rate), patients receiving higher opioid doses had a 3.7- and 8.9-fold increase (50–99 mg/day and 100 mg/day or greater, respectively) in overdose risk compared with patients who received low-dose opioids (1–20 mg/day) and a 0.7 and 1.8% annual overdose rate, respectively. Overdose rates were also higher in patients older than 65 years and patients with a history of depression or treatment of substance abuse. An increased overdose risk was also associated with shorter time to filling an original or refill prescription.
Although the number of overdoses in this study cohort was small, the study reinforces carefully selecting and closely monitoring patients who are prescribed opioids for chronic noncancer pain. Protocols, such as demonstration of improved quality of life before increasing dose, should be evaluated to attempt to reduce these preventable deaths in patients prescribed high-dose opioids for long-term pain management.
Prolonged sensory-selective nerve blockade. Proc Natl Acad Sci U S A 2010; 107:3740–5
The development and potential application of sensory-selective local anesthetics and long-acting local anesthetics could improve acute pain management and labor analgesia. Chemical permeation enhancers may allow for increased drug flux across cell membranes and hence increase the permeability of sensory selective drugs and the duration of nerve blockade.
This in vivo study tested the effect on thermal nociception of various concentrations of surfactants in combination with quaternary lidocaine derivatives such as QX-314 injected at the sciatic nerve of Sprague-Dawley rats. QX-314 demonstrated concentration-dependent durations of nerve blockade (approximately 1 day at 100 mm), and sensory selective nerve block occurred at some time points. The duration of sensory nerve block from 25 mm QX-314 was prolonged for up to 7 h in combination with a surfactant, 30 mm octyltrimethylammonium bromide (OTAB). Little or no motor block was observed. QX-314 in combination with varying concentrations of another surfactant, sodium octyl sulfate (SOS), produced prolongation of both sensory and motor blockade, but sensory selectivity was observed with 5 mm SOS. Sensory selectivity was imparted to varying degrees by cationic, neutral, and anionic surfactants and also was achieved with another quaternary lidocaine derivative, QX-222.
Local anesthetics used for producing prolonged nerve blockade have limitations and side effects including motor blockade. This study, using impermeant sodium channel blockers such as QX-314, suggests that adjuncts to local anesthetic mixtures, such as surfactants, may improve the sensory blockade profile of these drugs and permit better motor function during labor and after surgery.
Morphine use after combat injury in Iraq and posttraumatic stress disorder. N Engl J Med 2010; 362:110–7
It is common for seriously injured trauma survivors to experience posttraumatic stress disorder (PTSD). Recent research has focused on pharmacotherapy for secondary prevention of PTSD in the aftermath of serious physical injury or exposure to traumatic events. Decreasing or impeding memory consolidation with pharmacotherapy (e.g. , opiates, anxiolytics, and β-adrenergic antagonists) may play a role in reducing PTSD symptoms.
Using the US Navy–Marine Corps Combat Trauma Registry Expeditionary Medical Encounter Database, injured US military personnel (n = 696) were identified. Complete data on medications administered were available for all personnel selected. The diagnosis of PTSD was obtained from the Career History Archival Medical and Personnel System and verified in a review of medical records.
Among the 696 patients studied, 243 received a diagnosis of PTSD; 99% of which were men. The majority (90%) of injuries was not severe; however, the rates of serious injury and amputation were significantly higher in the PTSD-negative patients. No patients received selective serotonin-reuptake inhibitors or β-blockers. Benzodiazepines were not associated with the reduced onset of PTSD. Morphine was used in 61 and 76% of PTSD-positive and PTSD-negative patients, respectively, and was generally administered within 1 h of injury. Early morphine use was significantly associated with a lower risk of PTSD after injury (odds ratio, 0.47; P < 0.001) regardless of severity of injury, age, mechanism of injury, status with respect to amputation, injury-related clinical factors, or morphine dose.
The results of this observational study suggest that analgesic and other effects of opioids administered in the acute posttraumatic period reduce the incidence of PTSD. Other drugs and treatments during this period may also be factors. These data suggest that pharmacologic treatments in the acute posttraumatic period may have long-term benefits for trauma patients, including military personnel.
Suggested by: Hugh C. Hemmings, Jr., M.D., Ph.D.