Since 1967, 170 heroin addicts have used methadone-based maintenance therapy. The experimental programme, confined to the Uppsala Psychiatric Clinic, followed the Dole-Nyswander method. Evaluation of the results shows the therapy to be successful in reducing mortality and permanent disability rates in heroin users. In addition it was found that addicts included in the programme were more likely to achieve complete social rehabilitation. In spite of much criticism, the experiment was sufficiently successful to justify its continuation, though still within the limits and along the lines adopted in the past.
Sudden death due to acute intoxication occurs frequently in patients with opioid addiction (OA). To examine whether certain genotypes were associated with this, we examined the frequencies of 29 SNPs located in candidate genes related to opioid pharmacology: ABCB1, OPRM1, UGT2B7, CYP3A5, CYP2B6, CYP2C19, CYP2D6, COMT, KCNJ6 and SCN9A in 274 deceased patients with OA (DOA), 309 living patients with OA (LOA) and in 394 healthy volunteers (HV). The main hypothesis of the study was that subjects homozygous for the variant 3435T in ABCB1 (rs1045642) occur more frequently in DOA than in LOA and HV because morphine and methadone more readily cross the blood barrier in these subjects due to a lower efflux transporter activity of the ABCB1 (p-glycoprotein) transporter. Our results did not support this hypothesis, because no statistically significant difference (p = 0.506) in the frequency of the TT genotype of rs1045642 was observed between the DOA, LOA and HV cohorts. However, for another ABCB1 variant, rs9282564, we found that the frequencies of the AG and TT genotypes were 13, 21 and 25% in DOA, LOA and HV, respectively, and after correcting for age, sex and multiple testing, the differences between DOA and LOA were statistically significantly different (p = 0.027). The COMT rs4680 AA genotype frequencies were 25%, 35% and 31% in DOA, LOA and HV, respectively, and the difference between DOA and LOA was also statistically significant (p = 0.0028). In conclusion, this study generated two hypotheses suggesting possible associations of a reduced risk of death and carrying, respectively, the ABCB1 rs9282564 AG and TT genotypes and the COMT rs4680 AA genotype among patients with OA. These findings should be confirmed in independent cohorts, and if a causal relationship between these variants and fatal poisoning in OA is confirmed, then it may be possible at least in theory to personalize prevention of sudden death in this patient group.
From the *Department of Anaesthesia, Centre of Head and Orthopaedics, Copenhagen University Hospital, Rigshospitalet, Copenhagen; †Department of Anaesthesia, Frederiksberg Hospital, Copenhagen University Hospital, Frederiksberg; ‡Department of Anaesthesia, Glostrup Hospital, Copenhagen University Hospital, Glostrup; §Section of Acute Pain Management, Department of Anaesthesia, Centre of Head and Orthopaedics, Copenhagen University Hospital, Rigshospitalet, Copenhagen; and ?Department of Surgery, Glostrup Hospital, Copenhagen University Hospital, Glostrup, Denmark.
Femoral nerve block (FNB), a commonly used postoperative pain treatment after total knee arthroplasty (TKA), reduces quadriceps muscle strength essential for mobilization. In contrast, adductor canal block (ACB) is predominately a sensory nerve block. We hypothesized that ACB preserves quadriceps muscle strength as compared with FNB (primary end point) in patients after TKA. Secondary end points were effects on morphine consumption, pain, adductor muscle strength, morphine-related complications, and mobilization ability.
We performed a double-blind, randomized, controlled study of patients scheduled for TKA with spinal anesthesia. The patients were randomized to receive either a continuous ACB or an FNB via a catheter (30-mL 0.5% ropivacaine given initially, followed by a continuous infusion of 0.2% ropivacaine, 8 mL/h for 24 hours). Muscle strength was assessed with a handheld dynamometer, and we used the percentile change from baseline for comparisons. The trial was registered at clinicaltrials.gov (Identifier: NCT01470391).
We enrolled 54 patients, of which 48 were analyzed. Quadriceps strength as a percentage of baseline was significantly higher in the ACB group compared with the FNB group: (median [range]) 52% [31-71] versus 18% [4-48], (95% confidence interval, 8-41; P = 0.004). There was no difference between the groups regarding morphine consumption (P = 0.94), pain at rest (P = 0.21), pain during flexion of the knee (P = 0.16), or adductor muscle strength (P = 0.39); neither was there a difference in morphine-related adverse effects or mobilization ability (P > 0.05).
Adductor canal block preserved quadriceps muscle strength better than FNB, without a significant difference in postoperative pain.
The Swedish Society of Anaesthetists conducted a nationwide retrospective survey of clinical experience with extradural and intrathecal opiates. Special interest was focused on the frequency and type of ventilatory depression. The questionnaire was answered by 84 of 93 departments (90%). Up to May 1981 extradural morphine had been given to approximately 6000-9150 patients, extradural pethidine to 220-450 and intrathecal morphine to 90-150 patients. Ventilatory depression requiring treatment with naloxone was reported in 23 patients treated with extradural morphine (0.25-0.40%) and in six given intrathecal morphine (4-7%). In 22 patients the administration of extradural morphine was considered as a major contributory factor for the occurrence of ventilatory depression. Only two of these 22 patients experienced ventilatory depression later than 6 h after the last dose of opiates (S.C., i.m., i.v. or extradural). Patients aged 70 yr or more, those receiving thoracic extradural puncture and those with reduced ventilatory capacity seemed to be overrepresented.
The pharmacokinetics of morphine was studied in 27 infants receiving a single intravenous dose of 0.1 mg/kg morphine after surgery (n = 23) or during mechanical ventilation (n = 4). The pharmacokinetics of morphine varied greatly between the subjects, especially in the neonates. The clearance and half-life varied distinctly with postnatal age. The mean (+/- SD) half-life was 8.1 +/- 8.1 h in 10 neonates younger than 1 week, 5.4 +/- 3.4 h in 10 infants aged from 1 week to 2 months and 2.6 +/- 1.7 h in 7 infants aged from 2 to 6 months. Mean clearance increased significantly with age, being 8.7 +/- 5.8 ml/min/kg in the youngest age group, 11.9 +/- 5.1 ml/min/kg in those aged 1 week to 2 months and 28.0 +/- 8.9 ml/min/kg in those aged 2-6 months, and was also significantly lower in the critically ill infants. The clearance and half-life of morphine begin to approach adult values after the age of 1 month, but great individual variability exists even after that. In order to reduce the risk of overdosing or underdosing, the dose of morphine should be titrated individually.
Pulmonary vein isolation (PVI) is an established method for treatment of drug refractory atrial fibrillation. The aim of this study was to evaluate whether a more active regular supply of analgesic and sedative drugs reduces pain and discomfort. We also wanted to evaluate gender differences in pain perception and to compare standard radiofrequency (RF) with cryo balloon ablation (Cryo) from this perspective.
A total of 80 patients, 40 men, median age 58 (range 23-76) years, who underwent PVI under conscious sedation were studied. They were randomized to either standard treatment with morphine and diazepam (control group, C) or to a more active analgesic strategy (A) with pre-medication with oral midazolam mixture and intravenous alfentanil and midazolam regularly administrated during the procedure. Forty patients were treated with RF and 40 with Cryo.
The majority of the patients experienced pain during the procedure. The maximal pain assessed with numerical rating scale (NRS), was lower in the active group compared with that in controls (p = 0.02). Women experienced more pain than men (p = 0.01). RF was more painful than Cryo (p
Total knee arthroplasty (TKA) is associated with severe pain, and effective analgesia is essential for the quality of postoperative care and ambulation. The analgesic effects of adding an obturator nerve block (ONB) to a femoral triangle block (FTB) after TKA have not been tested previously. We hypothesized that combined ONB and FTB will reduce opioid consumption and pain compared with those of a single FTB or local infiltration analgesia (LIA).
Seventy-eight patients were randomized to combined ONB and FTB, single FTB, or LIA after primary unilateral TKA. The primary outcome was morphine consumption during the first 24 postoperative hours. Secondary outcomes included morphine consumption during the first 48 postoperative hours, pain at rest and passive knee flexion, nausea and vomiting, cumulated ambulation score, and Timed Up and Go test.
Seventy-five patients were included in the analysis. The total intravenous morphine consumption during the first 24 postoperative hours was 2 mg (interquartile range [IQR], 0-15) in the combined ONB and FTB group, 20 mg (IQR, 10-26) in the FTB group (P = 0.0007), and 17 mg (IQR, 10-36) in the LIA group (P = 0.002). The combined ONB and FTB group displayed reduced pain, nausea, and vomiting compared with the other groups. The ambulation tests showed no statistically significant differences between the groups.
Addition of ONB to FTB significantly reduced opioid consumption and pain after TKA compared with a single FTB or LIA, without impaired ambulation.
The paper deals with action efficiency of microbial biomass on characteristic indicators at alcohol and morphine organism intoxication. The investigated microbial biomass affects the regulatory biochemical and physiological systems in experimental animals, normalizes activity of alcohol dehydrogenase and aldehide dehydrogenase, as well as the content of dophamine, disturbed under the effect of alcohol and morphine. Thus, the organism intoxication decreases. Except for the specific action, the above microbial biomass can be a source of protein, aminoacids, vitamins, microelements. So, the microbial preparation, made on its basis, can be used for the treatment of alcohol and morphine dependence in a form of biologically active dope. Thus the microbial drug intended for treatment of alcohol and opium dependence has been developed. One of its action mechanisms is based on the microorganisms capacity to transform alcohols and aldehides, owing to availability of alcohol and aldehide dehydrogenase, other its action mechanisms are at the stage of investigation.