Self-intoxication with morphine obtained from an infusion pump.
(17/3881)
A 36-year-old Caucasian male was found unresponsive by his wife. He had white foam around his mouth and was pronounced dead shortly thereafter. He had a history of back pain and was treated with intrathecal morphine because of his previous addiction to oral opiate medications. Because of crimping of the pump catheter, it was replaced 4 days before his death. Toxicological findings included urine screen positive for amitriptyline, nortriptyline, opiates, hydrocodone metabolites, ibuprofen, acetaminophen, caffeine, nicotine, and metabolite. Drug concentrations were as follows: blood, 0.260 mg/L amitriptyline, 0.160 mg/L nortriptyline, 0.460 mg/L unconjugated morphine, and 0.624 mg/L total morphine; vitreous humor, 0.034 mg/L unconjugated morphine and 0.080 mg/L total morphine; and cerebrospinal fluid, 0.099 mg/L unconjugated morphine and 0.095 mg/L total morphine. Shortly after death, the volume of the residual pump reservoir was only 8 mL instead of the expected 17 mL. Testing by the FDA showed that the pump was functional. The residual content of the pump accounted for only 230 mg instead of the expected 488 mg. The high blood-morphine concentrations did not correlate with the intrathecal infusion dose. The symptoms were consistent with opiate overdose, possibly by injection of morphine withdrawn from the pump reservoir. The cause of death was determined to be fatal morphine self-intoxication, and the manner of death was accidental. This case is intended to alert regulatory agencies, pain management health professionals, pathologists, and toxicologists to the abuse potential of one of the newer analgesic-delivery systems. (+info)
Effect of i.v. ketamine in combination with epidural bupivacaine or epidural morphine on postoperative pain and wound tenderness after renal surgery.
(18/3881)
We studied 60 patients undergoing operation on the kidney with combined general and epidural anaesthesia, in a double-blind, randomized, controlled study. Patients were allocated to receive a preoperative bolus dose of ketamine 10 mg i.v., followed by an i.v. infusion of ketamine 10 mg h-1 for 48 h after operation, or placebo. During the first 24 h after surgery, all patients received 4 ml h-1 of epidural bupivacaine 2.5 mg ml-1. From 24 to 48 h after operation, patients received epidural morphine 0.2 mg h-1 preceded by a bolus dose of 2 mg. In addition, patient-controlled analgesia (PCA) with i.v. morphine (2.5 mg, lockout time 15 min) was offered from 0 to 48 h after operation. Patients who received ketamine felt significantly more sedated at 0-24 h, but not at 24-48 h after operation, compared with patients who received placebo (P = 0.002 and P = 0.127, respectively). There were no significant differences in pain (VAS) at rest, during mobilization or cough, PCA morphine consumption, sensory block to pinprick, pressure pain detection threshold assessed with an algometer, touch and pain detection thresholds assessed with von Frey hairs, peak flow or side effects other than sedation. The power of detecting a reduction in VAS scores of 20 mm in our study was 80% at the 5% significance level. We conclude that we were unable to demonstrate an (additive) analgesic or opioid sparing effect of ketamine 10 mg h-1 i.v. combined with epidural bupivacaine at 0-24 h, or epidural morphine at 24-48 h after renal surgery. (+info)
Dextromethorphan and pain after total abdominal hysterectomy.
(19/3881)
Dextromethorphan is an N-methyl-D-aspartate (NMDA) receptor antagonist which has been shown to inhibit the development of cutaneous secondary hyperalgesia after tissue trauma. We studied 60 ASA I-II patients undergoing total abdominal hysterectomy in a randomized, double-blind, placebo-controlled study. Patients received either dextromethorphan 27 mg capsules, two doses before operation and three doses in the first 24 h after operation, or placebo. Visual analogue pain scores (VAS) at 24 and 48 h were assessed at rest, on coughing and on sitting up, and were not significantly different between groups. Morphine consumption from a patient-controlled analgesia (PCA) device was also not significantly different between groups. Evidence of secondary hyperalgesia was assessed with von Frey hairs 10 cm above the Pfannenstiel incision. Both groups of patients exhibited evidence of secondary hyperalgesia after 24 and 48 h but there were no significant differences between groups. There was also no difference between groups in VAS scores at 1 month. (+info)
Tramadol or morphine administered during operation: a study of immediate postoperative effects after abdominal hysterectomy.
(20/3881)
Tramadol may cause awareness and EEG activation during anaesthesia. We compared tramadol with morphine, administered during wound-closure, surmising that tramadol may cause earlier awakening, more rapid recovery, less respiratory depression and equivalent pain relief. Forty patients received nitrous oxide-enflurane for abdominal surgery. At wound closure, patients received tramadol 3 mg kg-1 or morphine 0.2 mg kg-1 and end-tidal enflurane concentrations were maintained at 0.5 kPa until skin closure, whereupon anaesthesia was discontinued. Times to spontaneous respiration, awakening and orientation were similar in the two groups, as were blood-gas tensions, ventilatory frequency, pain scores and incidence of nausea. Half of each group required supplementary analgesia during their 90-min stay in the recovery room. P-deletion counts improved more rapidly in the tramadol group. This study confirms previous reports that tramadol did not antagonize the hypnotic effects of volatile anaesthetics. Tramadol, administered during operation, was as effective as morphine in providing postoperative analgesia while permitting more rapid psychomotor recovery. (+info)
Effects of prophylactic nalmefene on the incidence of morphine-related side effects in patients receiving intravenous patient-controlled analgesia.
(21/3881)
BACKGROUND: Opioid-related side effects associated with intravenous patient-controlled analgesia can be reduced by a low-dose naloxone infusion. The influence of nalmefene, a pure opioid antagonist with a longer duration of action, on opioid-related side effects has not been evaluated. This study was designed to determine the dose-response relation for nalmefene for the prevention of morphine-related side effects in patients receiving intravenous patient-controlled analgesia. METHODS: One hundred twenty women undergoing lower abdominal surgery were enrolled in the study. General anesthesia was induced using thiopental and rocuronium and maintained with desflurane, nitrous oxide, and fentanyl or sufentanil. All patients received neostigmine and glycopyrrolate to reverse residual neuromuscular blockade. No prophylactic antiemetics were administered. At the end of surgery, patients were randomized to receive saline, 15 microg nalmefene, or 25 microg nalmefene intravenously. The need for antiemetic and antipruritic drugs and the total consumption of morphine during the 24-h study were recorded. The incidences of postoperative nausea, vomiting, pruritus, and pain were recorded 30 min after patients were admitted to the postanesthesia care unit. In addition, patient remembrance of these side effects was noted at 24 h after operation. RESULTS: The need for antiemetic and antipruritic medications during the 24-h study period was significantly lower in the patients receiving nahmefene compared with those receiving placebo. However, the need to treat side effects was similar in the two nahmefene groups. Prophylactic administration of nalmefene reduced the patients remembrance of nausea and itching as assessed 24 h after operation. Although the total consumption of morphine during the 24-h study period was similar in the three groups, retrospectively patients who received nalmefene characterized their pain as less severe in the previous 24 h. CONCLUSION: Compared with placebo, prophylactic administration of nalmefene significantly decreased the need for antiemetics and antipruritic medications in patients receiving intravenous patient-controlled analgesia with morphine. (+info)
Pharmacokinetic modeling of M6G formation after oral administration of morphine in healthy volunteers.
(22/3881)
BACKGROUND: Morphine is metabolized to two major metabolites, morphine-3-glucuronide and morphine-6-glucuronide (M6G). Under the conditions of long-term oral morphine administration, the accumulation of M6G may contribute to the analgesic effects, but it may also cause respiratory depression. METHODS: Five healthy male volunteers (ages 25-34 yr) received 90 mg MST (morphine sulfate 5H2O sustained-released tablet, equivalent to 67.8 mg oral morphine). Multiple plasma and urine samples were taken for as long as 14 and 36 h, respectively. Individual pharmacokinetics after intravenous administration of morphine and M6G were available from a previous investigation. A new model that considers the M6G-plasma profile as a sum of the input from the first-pass metabolism of morphine and the input from systemically available morphine was applied to the plasma concentration versus time curves of M6G. The concentrations of M6G at the effect site after long-term morphine administration were simulated. RESULTS: The fraction of morphine absorbed from the gut was 82+/-14%. Of this, 42+/-8% passed through the liver, resulting in an oral bioavailability of morphine of 34+/-9%. Of the total amount of M6G, 71+/-7% was formed during the first-pass metabolism, and 29+/-7% was formed by metabolism of systemic morphine. After 36 h, the amounts of M6G and morphine excreted in the urine were 92+/-17% and 9+/-3%, respectively. Simulation of effect-site concentrations of M6G indicated that after multiple oral dosing of morphine in patients with normal liver and renal function, M6G might reach concentrations two times greater than that of morphine. CONCLUSIONS: M6G may contribute to the analgesic and side effects seen with long-term morphine treatment. The current model of morphine and M6G pharmacokinetics after oral administration of morphine may serve as a pharmacokinetic basis for experiments evaluating the analgesic contribution of M6G with long-term oral dosing of morphine. (+info)
Fentanyl and morphine, but not remifentanil, inhibit acetylcholine release in pontine regions modulating arousal.
(23/3881)
BACKGROUND: Opioids inhibit the rapid eye movement (REM) phase of sleep and decrease acetylcholine (ACh) release in medial pontine reticular formation (mPRF) regions contributing to REM sleep generation. It is not known whether opioids decrease ACh release by acting on cholinergic cell bodies or on cholinergic axon terminals. This study used in vivo microdialysis to test the hypothesis that opioids decrease ACh levels at cholinergic neurons in the laterodorsal tegmental nuclei (LDT) and LDT axon terminals in the mPRF. METHODS: Nine male cats were anesthetized with halothane, and ACh levels within the mPRF or LDT were assayed using microdialysis and high-pressure liquid chromatography (HPLC). ACh levels were analyzed in response to dialysis of the mPRF and LDT with Ringer's solution (control), followed by dialysis with Ringer's solution containing morphine sulfate (MSO4) or naloxone. ACh in the mPRF also was measured during either dialysis delivery or intravenous infusion of remifentanil and during dialysis delivery of fentanyl. RESULTS: Compared with dialysis of Ringer's solution, microdialysis with MSO4 decreased ACh by 23% in the mPRF and by 30% in the LDT. This significant decrease in ACh was antagonized by naloxone. MSO4 and fentanyl each caused a dose-dependent decrease in mPRF ACh when delivered by dialysis. Remifentanil delivered by continuous intravenous infusion or by dialysis into the mPRF did not alter mPRF ACh. CONCLUSIONS: Morphine inhibits ACh at the cholinergic cell body region (LDT) and the terminal field in the mPRF. ACh in the mPRF was not altered by remifentanil and was significantly decreased by fentanyl. Thus, MSO4 and fentanyl disrupt cholinergic neurotransmission in the LDT-mPRF network known to modulate REM sleep and cortical electroencephalographic activation. These data are consistent with the possibility that inhibition of pontine cholinergic neurotransmission contributes to arousal state disruption by opioids. (+info)
Effect of systemic morphine on the responses of convergent neurons to noxious heat stimuli applied over graded surface areas.
(24/3881)
BACKGROUND: Stimulus intensity is a major determinant of the antinociceptive activity of opiates. This study focused on the influence of the spatial characteristics of nociceptive stimuli, on opiate-induced depressions of nociceptive transmission at the level of the spinal cord. METHODS: Anesthetized rats were prepared to allow extracellular recordings to be made from convergent neurons in the lumbar dorsal horn. The effects of systemic morphine (1 and 10 mg/kg) were compared with those of saline for thermal stimuli of constant intensity, applied to the area of skin surrounding the excitatory receptive field (1.9 cm2) or to a much larger adjacent area (18 cm2). RESULTS: The responses (mean +/- SD) elicited by the 1.9-cm2 stimulus were not modified by 1 mg/kg intravenous morphine, although they were decreased by the 10-mg/kg dose (to 11+/-4% of control values compared with saline; P < 0.05). In contrast, when the 18-cm2 stimulus was applied, 1 mg/kg intravenous morphine produced a paradoxical facilitation of the neuronal responses (159+/-36% of control values; P < 0.05) and 10 mg/kg intravenous morphine resulted in a weaker depression of the responses (to 42+/-24% of control values; P < 0.05) than was observed with the smaller stimulus. CONCLUSIONS: Doses of systemic morphine in the analgesic range for rats had dual effects on nociceptive transmission at the level of the spinal cord, depending on the surface area that was stimulated. Such effects are difficult to explain in terms of accepted pharmacodynamic concepts and may reflect an opioid-induced depression of descending inhibitory influences triggered by spatial summation. (+info)