Benefit and harm of pregabalin in acute pain treatment: a systematic review with meta-analyses and trial sequential analyses.

Pregabalin has demonstrated anti-hyperalgesic properties and was introduced into acute pain treatment in 2001. Our aim was to evaluate the beneficial and harmful effects of pregabalin in postoperative pain management. We included randomized clinical trials investigating perioperative pregabalin treatment in adult surgical patients. The review followed Cochrane methodology, including Grading of Recommendations Assessment, Development, and Evaluation (GRADE), and used trial sequential analyses (TSAs). The primary outcomes were 24 h morphine i.v. consumption and the incidence of serious adverse events (SAEs) defined by International Conference of Harmonisation Good Clinical Practice guidelines. Conclusions were based primarily on trials with low risk of bias. Ninety-seven randomized clinical trials with 7201 patients were included. The 24 h morphine i.v. consumption was reported in 11 trials with overall low risk of bias, finding a reduction of 5.8 mg (3.2, 8.5; TSA adjusted confidence interval: 3.2, 8.5). Incidence of SAEs was reported in 21 trials, with 55 SAEs reported in 12 of these trials, and 22 SAEs reported in 10 trials with overall low risk of bias. In trials with overall low risk of bias, Peto's odds ratio was 2.9 (1.2, 6.8; TSA adjusted confidence interval: 0.1, 97.1). Based on trials with low risk of bias, pregabalin may have a minimal opioid-sparing effect, but the risk of SAEs seems increased. However, the GRADE-rated evaluations showed only moderate to very low quality of evidence. Consequently, a routine use of pregabalin for postoperative pain treatment cannot be recommended.

Gabapentin for post-operative pain management - a systematic review with meta-analyses and trial sequential analyses.

BACKGROUND: Perioperative pain treatment often consist of combinations of non-opioid and opioid analgesics, 'multimodal analgesia', in which gabapentin is currently used. The aim was to document beneficial and harmful effects of perioperative gabapentin treatment. METHODS: Randomized clinical trials comparing gabapentin vs. placebo or active placebo in adult surgical patients receiving gabapentin perioperatively were included. This review was conducted using Cochrane standards, trial sequential analysis (TSA), and Grading of Recommendations Assessment, Development, and Evaluation (GRADE). The primary outcomes were 24-h opioid consumption and incidence of serious adverse events (SAE). RESULTS: One hundred and thirty-two trials with 9498 patients were included. Thirteen trials with low risk of bias reported a reduction in 24-h opioid consumption of 3.1 mg [0.5, 5.6] [corrected]. In the analysis of gabapentin as add-on analgesic to another non-opioid analgesic regimen found a mean reduction in 24-h morphine consumption of 1.2 mg [-0.3, 2.6; TSA-adjusted CI: -0.3, 2.6] in trials with low risk of bias. [corrected]. Nine trials with low risk of bias reported a risk ratio of SAEs of 1.61 [0.91; 2.86; TSA-adjusted CI: 0.57, 4.57]. CONCLUSION: Based on GRADE assessment of the primary outcomes in trials with low risk of bias, the results are low or very low quality of evidence due to imprecision, inconsistency, and in some outcomes indirectness. Firm evidence for use of gabapentin is lacking as clinically relevant beneficial effect of gabapentin may be absent and harm is imminent, especially when added to multimodal analgesia.

Transversus abdominis plane (TAP) block after robot-assisted laparoscopic hysterectomy: a randomised clinical trial.

BACKGROUND: Transversus abdominis plane (TAP) block is widely used as a part of pain management after various abdominal surgeries. We evaluated the effect of TAP block as an add-on to the routine analgesic regimen in patients undergoing robot-assisted laparoscopic hysterectomy. METHODS: In a prospective blinded study, 70 patients scheduled for elective robot-assisted laparoscopic hysterectomy were randomised to receive either TAP block (ropivacaine 0.5%, 20 ml on each side) or sham block (isotonic saline 0.9%, 20 ml on each side). All patients had patient-controlled analgesia (PCA) with morphine on top of paracetamol and ibuprofen or diclofenac. For the first 24 post-operative hours, we monitored PCA morphine consumption and pain scores with visual analogue scale (VAS) at rest and while coughing. Post-operative nausea and number of vomits (PONV) were recorded. RESULTS: Sixty-five patients completed the study, 34 receiving TAP block with ropivacaine and 31 receiving sham block with isotonic saline. We found no differences in median (interquartile range) morphine consumption the first 24 h between the TAP block group [17.5 mg (6.9-36.0 mg)] and the placebo group [17.5 mg (2.9-38.0 mg)] (95% confidence interval 10.0-22.6 mg, P = 0.648). No differences were found for VAS scores between the two groups, calculated as area under the curve/1-24 h, neither at rest (P = 0.112) nor while coughing (P = 0.345), or for PONV between groups. CONCLUSIONS: In our study, the TAP block combined with paracetamol and Nonsteroidal anti-inflammatory drugs (NSAID) treatment, had no effect on morphine consumption, VAS pain scores, or frequency of nausea and vomiting after robot-assisted laparoscopic hysterectomy compared with paracetamol and NSAID alone.

The transversus abdominis plane block: a valuable option for postoperative analgesia? A topical review.

The transversus abdominis plane (TAP) block is a newly described peripheral block involving the nerves of the anterior abdominal wall. The block has been developed for post-operative pain control after gynaecologic and abdominal surgery. The initial technique described the lumbar triangle of Petit as the landmark used to access the TAP in order to facilitate the deposition of local anaesthetic solution in the neurovascular plane. Other techniques include ultrasound-guided access to the neurovascular plane via the mid-axillary line between the iliac crest and the costal margin, and a subcostal access termed the 'oblique subcostal' access. A systematic search of the literature identified a total of seven randomized clinical trials investigating the effect of TAP block on post-operative pain, including a total of 364 patients, of whom 180 received TAP blockade. The surgical procedures included large bowel resection with a midline abdominal incision, caesarean delivery via the Pfannenstiel incision, abdominal hysterectomy via a transverse lower abdominal wall incision, open appendectomy and laparoscopic cholecystectomy. Overall, the results are encouraging and most studies have demonstrated clinically significant reductions of post-operative opioid requirements and pain, as well as some effects on opioid-related side effects (sedation and post-operative nausea and vomiting). Further studies are warranted to support the findings of the primary published trials and to establish general recommendations for the use of a TAP block.

[Maternal serum screening for congenital abnormalities and Down syndrome in Sønderjylland County. Eight years of experience]. / Maternel serumscreening for medfødte misdannelser og Downs syndrome i Sønderjyllands Amt. Otte års erfaringer.

From January 1991 to December 1998 second-trimester maternal serum screening (Doubletest and Tripletest) for malformations and Down syndrome has been offered to pregnant women younger than 35 years of age living in Sønderjyllands county, Denmark. Follow-up of all cases of chromosome abnormalities and severe foetal malformations identified pre- or postnatally has been carried out. A total of 17,023 women were screened. Sixty-eight percent (17/25) of Down Syndrome pregnancies were detected. Three percent of the screened women were offered an amniocentesis due to a calculated risk of DS greater than 1:400 at birth. The positive predictive value was 1:30. For the three-year period 1996-1998 (Tripletest) the results were more promising: 91% (10/11) were detected, 3.9% were offered an amniocentesis, the positive predictive value was 1:21. In the eight-year period 80% (8/10) of the spina bifida cases were detected, all the cases (6/6) of anencephaly and 75% (6/8) of abdominal wall defects. One point six percent of the screened women were offered an amniocentesis due to high risk of a neural tube defect. The results confirm that second trimester maternal serum screening is a reliable method for determining the risk of severe foetal malformations and Down syndrome.

Reduced albumin binding of MADDS--a measure of bilirubin binding--during pregnancy and delivery.

It was the purpose of the present study to investigate whether the decrease in the ability of plasma albumin to bind bilirubin, noted in pregnancy and during delivery, takes place in one step, during pregnancy alone, or in two steps, during both pregnancy and delivery. Furthermore, it was investigated whether a possible decrease during labor was related to the method of delivery itself. The material comprised (a) 17 pregnant women who delivered vaginally; (b) 25 women who were delivered by Cesarean Section; and (c) a group of 25 non-pregnant women. The reserve albumin concentration for binding of MADDS (a measure of the binding of unconjugated bilirubin), the total albumin concentration and the ratio between them were constant in the 6-week period up to birth and were significantly lower than the corresponding values in the non-pregnant group. During labor a significant decrease in reserve albumin and ratio of reserve albumin to total albumin was observed, while no change in the total albumin concentration was noted. No significant difference in reserve albumin concentration, total albumin concentration and ratio between them was found when the group of mothers who delivered vaginally was compared to the Cesarean Section group. It is concluded that the decrease in the ability of plasma albumin to bind unconjugated bilirubin takes place stepwise. The first step is a significant reduction during pregnancy followed by a further decrease during labor. The method of delivery is of no significance.

Neurogenic pulmonary edema: treatment with dobutamine.

In the case of a patient with complicating subarachnoid hemorrhage, an infusion of dobutamine was followed by a massive diuresis and regression of severe neurogenic pulmonary edema. It is suggested that the reduction in total peripheral vascular resistance and the increase in cardiac contractility accounts for the observed beneficial effect and indicate that dobutamine is a suitable drug for the treatment of neurogenic pulmonary edema.

Xanthine and hypoxanthine in amniotic fluid during pregnancy.

Xanthine and hypoxanthine are indicators of cellular hypoxia. The purpose of our study was to establish a reference range for the concentrations of xanthine and hypoxanthine in amniotic fluid. Of a total of 38 included in the investigation, 27 pregnant women were found to have low values for xanthine (less than 1.2 mumol/l) and hypoxanthine (less than 0.4 mumol/l). To our knowledge, this is the first attempt to define a reference range for xanthine and hypoxanthine concentration in amniotic fluid during pregnancy.