The specific effects of prior opioid exposure on placebo analgesia and placebo respiratory depression

Although in most of the cases the placebo response appears to be unpredictable, several factors have been considered in order to explain the placebo analgesic effect. For example, it is widely recognized, albeit with little empirical evidence, that placebo analgesia is more likely to occur after a successful analgesic therapy. On the basis of this assumption, we tested the placebo response in a population of patients who were treated with buprenorphine the day before for relieving postoperative pain. However, due to the high variability of opioid responsiveness, buprenorphine was effective in some patients and poorly effective in some others. Similarly, buprenorphine produced respiratory depression with a large variability, ranging from mild depression to no effect. We found that the placebo analgesic response depended on the buprenorphine analgesic effectiveness of the previous day. Analogously, we found that a placebo respiratory depressant response was more pronounced in those patients with a respiratory depressant response to buprenorphine on the day before, irrespective of the analgesic effectiveness. These specific effects suggest that (1) the placebo effect is experience-dependent; (2) the mechanisms underlying placebo analgesia and placebo respiratory depression are independent from each other and, by considering the role of endogenous opioids in placebo analgesia, might involve different subpopulations of opioid receptors.     

Comparative study of postoperative analgesia with methadone and fentanyl in continuous peridural perfusion

OBJECTIVE: To determine whether continuous epidural perfusion of fentanyl, which is more liposoluble than methadone, provides a similar level of analgesia with fewer side effects than methadone administered by the same route for postoperative pain. PATIENTS AND METHODS: Prospective double blind study of 40 patients, randomly assigned to two groups. Group F (n = 20) received 300 micrograms-1200 micrograms/24 h in epidural perfusion. Group M (n = 20) received 9 mg-18 mg/24 h in epidural perfusion. In both cases treatment was for pain in the first 72 h after abdominal surgery. Analgesia quality was evaluated on a visual analog (VAS) scale from 1 to 10 at rest and moving. Need for complementary analgesia was also recorded, as were side effects related to the technique. RESULTS: Quality of analgesia was good and similar which both drugs. Postoperative pain did not surpass 3 on the VAS at rest or 4.5 while moving, although group F patients' need for complementary analgesia was significantly greater (p < 0.05). The incidence of hypoxemia was greater in group M than in group F (p = 0.05). CONCLUSIONS: Continuous epidural perfusion of fentanyl provides good analgesia and is associated with less hypoxemia than is methadone.     

Diclofenac analgesia following cleft palate surgery

OBJECTIVE: This prospective study looked at the postoperative hemorrhage risk associated with the use of diclofenac following cleft palate repair. PATIENTS: Twenty consecutive children (6 months to 9 years of age) requiring repair of the hard or soft palate were included. DESIGN AND METHODS: Single per rectum doses of diclofenac were given at 1 mg/kg following cleft palate repair, with additional doses every 12 hours. RESULTS AND CONCLUSIONS: The use of the nonsteroidal anti-inflammatory drug, diclofenac, for postoperative analgesia is well established for many types of surgery. The authors find that twice daily diclofenac rectal suppositories provide very good analgesia postcleft palate repair. This, combined with supplemental oral paracetamol, obviates the need for opiates, resulting in alert infants who feed well and are suitable for early discharge.     

Prolonged survival following cerebral metastasis from pulmonary cancer

A case is reported of prolonged survival after pneumonectomy for anaplastic carcinoma of the left lung and excision of metastatic anaplastic carcinoma of the brain. The patient has survived for 8 years, 6 months after the lung surgery and 7 years after the brain surgery.     

Reduction of stress-induced analgesia following ethanol exposure in mice

In the present study, we examined the effects of ethanol treatment on the subsequent expression of opioid and nonopioid forms of swim stress-induced analgesia (SSIA). In Experiment 1, mice were injected with ethanol (2.5 g/kg, i.p.) or an equal volume of saline once a day for two days. Animals received no treatment on day 3. On day 4, the animals were tested for opioid (3-min swim in water maintained at 32 degrees C) or nonopioid (3-min swim in water maintained at 20 degrees C) SSIA in the hotplate test (52 degrees C). Mice pretreated with ethanol injections showed a decrease in nonopioid SSIA, but not in opioid SSIA. In Experiment 2, mice were given an ethanol solution (10%) or tap water to drink for 15 days. On day 16, all animals were given tap water to drink. On day 17, the animals were tested for opioid or nonopioid SSIA. Neither form of SSIA was modified in mice that drank the ethanol solution. These results show that ethanol pretreatment can modify nonopioid endogenous analgesic responses in mice. Further, the route of administration influences the effects of ethanol pretreatment on SSIA.     

Response to methadone maintenance and counseling in antisocial patients with and without major depression

This study compared the treatment response of four groups of psychiatrically diverse opiate-dependent, methadone maintenance patients receiving drug counseling. The four groups were patients with no other nonsubstance abuse axis I psychiatric diagnoses (OP only; N = 65), patients with lifetime major depression (DEP; N = 60), patients with both antisocial personality disorder and lifetime major depression (APD + DEP; N = 35), and patients with only APD (APD only; N = 24). Patients were assessed at intake, during treatment, and 7 months after treatment admission. No statistically significant differences were found among the groups in treatment retention/attendance. Few significant group differences were revealed during-treatment urine screens, except that barbiturate use was more common for the APD only group. The APD only group also had significantly more positive urine screens for benzodiazepines than the other three groups at 7-month follow-up. All groups reported considerable improvement in problem level at 7 months compared with admission status. The APD only group reported fewer gains in legal and employment problems than the other groups but reported greater improvement in the drug area. Thus, there was some limited support for a prior finding, based on individual psychotherapy, that the treatment response of APD only patients was inferior to that of APD + DEP patients or non-APD patients.     

Fetal heart rate following coelocentesis

For psychological reasons, coelocentesis was performed in 20 women prior to termination of pregnancy, at 6-11 weeks of gestation. The fetal heart rate (FHR) was measured immediately before the procedure and at 1, 5, and 10 min afterward. There was no significant difference between FHR before coelocentesis compared to the values at 1 min (mean = 158, range 114-178; z = -0.629, P = 0.529), 5 min (mean = 160, range 121-179; z = -0.191, P = 0.848), or 10 min (mean 159, range 117-183; z = -0.214, P = 0.83) after the procedure. These findings suggest that coelocentesis does not have a major effect on the fetal cardiovascular system.     

Evaluation of post-operative analgesia following laparoscopic application of Filshie clips

OBJECTIVE: To evaluate the efficacy of injecting 1% lignocaine into the subserosal aspect of the cornual end of the fallopian tubes to control post-operative pain after laparoscopic Filshie clip application. DESIGN: A double blind, randomised controlled trial. SETTING: The day surgery unit of the Dunedin Public Hospital, Otago, New Zealand. PARTICIPANTS: Fifty-nine women attending the public hospital requesting sterilisation. INTERVENTIONS: The experimental group received an infiltration of 1% lignocaine into the subserosal aspect of the cornual end of the fallopian tubes. The control group received an infiltration of normal saline in the same site. MAIN OUTCOME MEASURES: The use of post-operative pethidine and the scores obtained on a modification of the McGill present pain intensity score, a visual analogue scale of present pain, a pain relief score and comparisons of time to first analgesia use. RESULTS: The use of pethidine in the experimental group was significantly reduced [P = 0.001] Pain relief scores indicated significant benefit from the intervention. The time to first analgesic use was significantly greater in the experimental group. CONCLUSION: Lignocaine infiltration at the cornual end of the fallopian tubes during laparoscopic Filshie clip application is highly effective in producing post-operative pain relief.     

Components of respiratory depression after narcotic premedication in adolescents

The biliary and urinary excretion and the choleretic effect of ioglycamide were studied in unanesthetized bile fistula dogs using stepwise increasing infusion rates to obtain multiple steady states. The results are compared with data from previously reported experiments in the same animals using iodoxamate and iodipamide. The rate of biliary excretion and the choleretic effect of ioglycamide are similar to those of iodipamide and iodoxamate. Like iodipamide and iodoxamate, the relation between infusion rate or plasma concentration and biliary excretion or concentration of ioglycamide are hyperbolic and can be fitted to saturation kinetics. Quantitatively, the excretion of ioglycamide and iodipamide are virtually identical. However, for any equimolar infusion rate or plasma concentration, more iodoxamate than ioglycamide is excreted in the bile. Despite the greater biliary excretion of iodoxamate, the maximum biliary concentration of ioglycamide, iodipamide, and iodoxamate is the same at low basal bile flow because the choleretic effects of the three compounds are equal. The data suggest that, theoretically, with any equimolar dose ioglycamide will be identical to iodipamide as a contrast material for intravenous cholangiography, but that iodoxamate may be superior to ioglycamide because more iodoxamate is excreted in the bile. This advantage of iodoxamate might become apparent clinically in patients with high basal bile flow or if smaller doses of the contrast material are used. However, at the presently recommended doses of the two compounds, it is unlikely that the use of ioglycamide for intravenous cholangiography will be any different than iodoxamate.     

Endotracheal naloxone reversal of morphine-induced respiratory depression in rabbits

In an emergency, intravenous access may be difficult to obtain rapidly. Alternate routes of administration for drugs are, therefore, desirable. Our study was performed to determine if naloxone could be efficacious in reversing morphine-induced respiratory depression in rabbits when administered using the endotracheal route. Our results indicate that naloxone administered in this fashion is effective in reversing morphine-induced respiratory depression in the rabbit. Mean minute ventilation was depressed to greater than half of resting baseline levels using morphine sulfate. Endotracheally administered naloxone reversed this respiratory depression and resulted in a greater than five-fold increase in mean minute ventilation above baseline levels. We concluded that endotracheal naloxone is efficacious in reversing morphine-induced respiratory depression in the rabbit. The endotracheal route may be an effective alternative for naloxone administration in man when rapid intravenous access is not obtainable.     

Respiratory depression associated with patient-controlled analgesia: a review of eight cases

Patient-controlled iv delivery of opioids for postoperative pain management is a popular alternative to the traditional im route of administration. However, occasional patients receiving opioids in this manner develop severe respiratory depression. The purpose of this paper is to determine the incidence of, and factors contributing to, the development of this complication. To do this, the Office of Medical Quality Improvement retrospectively searched for reports of respiratory depression in a database compiled from the charts of approximately 1600 patients who had received PCA at the University of Alberta Hospitals in 1992. Eight cases of serious respiratory depression were detected. Factors associated with the occurrence of respiratory depression included the concurrent use of a background infusion, advanced age, concomitant administration of sedative/hypnotic medications, and pre-existing sleep apnoea syndrome. No cases were attributed to operator error or equipment malfunction. In conclusion, the risk of respiratory depression with patient-controlled opioid administration is similar to that observed when opioids are delivered by the traditional im or spinal routes. The safe and effective use of patient-controlled analgesia depends upon knowledgeable medical and nursing staff, clearly defined nursing policy and procedures, and frequent patient follow-up.     

Unconditioned stress-induced analgesia following exposure to brief footshock.

Four experiments, with 136 male Sprague-Dawley rats, examined the properties of unconditioned analgesia elicited by electric footshock stimuli using UCS parameters typical of aversive conditioning paradigms. In all experiments, analgesia was inferred from the latency to paw lick in response to painful thermal stimulation in the hot-plate assay. In Exp I, Ss exposed to a 1-sec, 2-mA shock UCS showed significantly longer latencies to respond to painful thermal stimulation than nonshocked controls, whereas nonsignificant increases in response latencies were observed with 1-sec shock UCS of either 0.5 or 1.25 mA. In Exp II, Ss exposed to a 2-mA electric shock UCS showed systematic increases in latencies to respond to painful thermal stimulation as the duration of the shock was varied between 0.5 and 2 sec. Exp III showed that this form of shock-induced analgesia was of short temporal duration. Specifically, significant increases in latencies to respond to painful thermal stimulation occurred 30 but not 90 or 300 sec following exposure to shock. Exp IV demonstrated that this form of analgesia was unaffected by pretreatment with the opiate receptor antagonist naloxone HCl in ip dosages of 1, 5, 10, or 20 mg/kg. Finally, there was no evidence showing that environmental stimuli paired with shock presentations acquired the capacity to evoke analgesia as a conditioned response. Implications of shock-induced analgesia for the study of aversive conditioning and behavior are discussed. (26 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The determinants of respiratory rate during mechanical ventilation

The independent and interactive effect of feedback related to volume, CO2, inspiratory flow, and arousal state on the regulation of respiratory rate in mechanically ventilated humans is not well characterized. We examined the rate response of eight normal volunteers during both quiet wakefulness and non-rapid-eye-movement (NREM) sleep, while mechanically ventilated through a nasal mask in an assist/control mode with a machine back-up rate of 2 breaths/min. Tidal volume (VT) was set slightly above spontaneous VT and then increased by 0.2 L every 3 min up to 1.8 L or 25 ml/kg. Either an inspiratory flow of 40 L/min or an inspiratory time of 2 s (iso-T(I)) was set, with CO2 added (F(I)CO2 > 0) or F(I)CO2 = 0. Measurements were made during both quiet wakefulness and NREM sleep. We found that as VT increased, the respiratory rate decreased; the rate decline was observed during wakefulness and sleep, and under isocapnic as well as hypocapnic conditions. Increasing inspiratory flow raised the respiratory rate during wakefulness and NREM sleep. During NREM sleep, hypocapnia resulted in wasted ventilator trigger efforts. In summary, both VT and inspiratory flow settings affect the respiratory rate, and depending on state, can affect CO2 homeostasis. Ventilator settings appropriate for wakefulness may cause ventilatory instability during sleep.     

Correcting respiratory rate for the presence of fever

This study defines what degree of respiratory rate (RR) elevation can be attributed to fever using a double blind randomized pre- and post-acetaminophen comparison of vital signs of febrile children presenting to an outpatient clinic. Inclusion criteria were aged between 6 weeks and 24 months, fever between 38.5 and 40.1 degrees C, no serious illness such as sepsis, and no recent receipt of antipyretics or antibiotics. RRs counted over 1 min and rectal temperatures were recorded by a trained observer before, and 1 and 1.5 hours (hr) after receipt of 10-15 mg/kg/dose of either acetaminophen (A) or placebo (P). Randomization produced groups A (n = 54), and P (n = 50) with similar mean age (12.3 vs 12.8 mo.), gender distribution (57 vs 54% female), baseline temperature (39.1 vs 39.1 degrees C), baseline RR (44 vs 45), and hours of fever prior to visit (42 vs 37 hr). The most common diagnoses were otitis media (49%), viral syndrome (18%), upper respiratory infection (16%) or gastroenteritis (7%). The mean temperature decrement of group A was 0.4 degrees C at 1 hr and 0.9 degrees C at 1.5 hr compared to slight increases in fever of 0.3 degrees C at 1 hr and 1.5 hr in group P. Significant decreases in RR occurred in group A compared to group P at 1 hr (7.0 vs 1.9, p = 0.009) and 1.5 hr (10.8 vs 4.0, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

The many faces of depression following spousal bereavement

While it is becoming increasingly clear that mood disorders tend to be chronic, intermittent and/or recurrent conditions with different manifestations over time, little is known of the variability or course of mood disorders that are associated with severe psychosocial stress. This paper reports on the prevalence and course of major, minor, and subsyndromal depressions in 328 widows and widowers followed prospectively from 2 to 25 months following one of the most disruptive of all naturally occurring stressors, spousal bereavement. The results are consistent with the following conclusions: (1) past major depression (prior to the death) predicts an increased risk for major depression following bereavement; (2) membership in any of the unipolar subgroups, in turn, predicts future depression throughout the unipolar depressive spectrum; (3) subsyndromal and minor depression stand between major depression, on the one hand, and no depression, on the other, in terms of their effects on overall adjustment to widowhood. Thus, the results support the validity of subsyndromal depression, and that the three subgroups (major, minor and subsyndromal depression) are pleiomorphic manifestations of the same unipolar depression disorder.