Extracorporeal membrane oxygenation in adult patients with severe acute respiratory failure.

BACKGROUND: A group of patients with severe acute respiratory distress syndrome (ARDS) is resistant to advanced respiratory therapy. In these patients, extracorporeal membrane oxygenation (ECMO) can be used as a rescue therapy. This study presents 14 years of experience from a Scandinavian ECMO centre. The aim of the study is to present outcome results and to investigate whether or not simplified acute physiology score II (SAPS-II), sequential organ failure assessment (SOFA) and/or Murray scores can be used to predict patients' outcome. METHODS: In a prospective observational study, we collected data from ECMO patients from January 1997 to March 2011. The treatment was based mainly on venous-venous ECMO and centrifugal pumps. Patients were retrieved from Denmark plus a number from Sweden and Norway. The inclusion criteria were the classical criteria until November 2009 (n = 100), after which the new Extracorporeal Life Support Organisation criteria (n = 24) were used. RESULTS: One hundred and twenty-four patients were enrolled with median age 45 (range 16-67) years. The median Murray score was 3.7 (2.5-4.0). One hundred and six (85%) of the patients were retrieved from referring hospitals on ECMO. The median duration of the ECMO runs was 215 (1-578) h. Ninety-seven (78%) of the patients could be weaned from ECMO. A total of 88 (71%) were discharged alive to the referring hospitals. High SAPS-II, SOFA and Murray scores were associated with a high mortality. CONCLUSION: Patients with severe ARDS have a favourable outcome when treated with ECMO and when an ECMO retrieval team establishes the ECMO treatment at the referring hospital. SAPS-II, SOFA and Murray scores predicted the outcome.

Relationship between mechanical sensitivity and postamputation pain: a prospective study.

Limb amputation is followed by stump and phantom pain in a large proportion of amputees and postamputation pain may be associated with signs of hyperexcitability such as hyperalgesia to mechanical stimulation. The present study examined the possible relationship between mechanical pain threshold of the limb and early (after 1 week) and late (after 6 months) phantom pain. Thirty-five patients scheduled for amputation of the lower limb were examined before, 1 week and 6 months after amputation. On all three examination days pressure-pain thresholds were measured and compared with the simultaneous recording of ongoing pain intensity assessed on a visual analogue scale (VAS). There was a weak but significant inverse relationship between preamputation thresholds and early stump and phantom pain. There was no relationship between preamputation thresholds and late stump and phantom pain. One week after amputation there was a significant and inverse relationship between mechanical thresholds and phantom pain but no relationship was found after 6 months. The findings suggest that although tenderness of the limb before and after amputation is related to early stump and phantom pain, the relationship is weak. Neuronal sensitization peripherally or centrally may play a role in the development of phantom pain.

The effect of dextromethorphan, alone or in combination with ibuprofen, on postoperative pain after minor gynaecological surgery.

BACKGROUND: Experimental studies have demonstrated that peripheral tissue injury may lead to hyperexcitability of nociceptive neurones in the dorsal horn, in part mediated by N-methyl-D-aspartate (NMDA)-receptor mechanisms. Sensitisation of dorsal horn neurones may be an important contributor to postoperative pain. The aim of the present study was to investigate the effect of the NMDA-receptor antagonist dextromethorphan on pain after minor gynaecological surgery, and to evaluate a potential additive effect with ibuprofen. METHODS: In a double-blind, placebo-controlled study, 100 patients scheduled for elective termination of pregnancy were randomised to receive placebo, oral ibuprofen 400 mg, oral dextromethorphan 120 mg, or a combination of ibuprofen 400 mg and dextromethorphan 120 mg, 1 h before surgery. Pain and analgesic requirements were assessed 0.5, 1 and 2 h after operation. RESULTS: We observed no effect of dextromethorphan on visual analogue scale (VAS) pain scores or analgesic consumption, and no additive or synergistic analgesic effects between ibuprofen and dextromethorphan. Ibuprofen reduced pain scores compared with placebo, and analgesic consumption compared with both placebo and dextromethorphan. The combination of ibuprofen and dextromethorphan increased preoperative nausea compared with both placebo and ibuprofen, whereas no statistically significant side effects were observed with dextromethorphan alone. CONCLUSION: No analgesic effects of oral dextromethorphan 120 mg on pain after surgical termination of labour, and no additive analgesic effects when combined with ibuprofen 400 mg, were observed. Ibuprofen reduced both VAS pain scores and analgesic consumption compared with placebo.

Effect of preoperative oral dextromethorphan on immediate and late postoperative pain and hyperalgesia after total abdominal hysterectomy.

Dextromethorphan is a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist known to inhibit wind-up and NMDA-mediated nociceptive responses of dorsal horn neurons. Experimental and clinical studies indicate that NMDA-receptor antagonists may potentiate the effect of analgesics such as morphine, local anesthetics and NSAIDs. Results from previous clinical studies of dextromethorphan in postoperative pain are conflicting, possibly related to administration of insufficient doses of the drug. Fifty patients scheduled for non-malignant elective abdominal hysterectomy in general anesthesia were randomized to receive oral dextromethorphan 150 mg, or placebo 1 h before surgery. The patients received patient-controlled analgesia with morphine for 24 h postoperatively as the only analgesic. Patient-controlled analgesia (PCA) morphine consumption was reduced with 30% from 0-4 h after operation in patients receiving dextromethorphan compared with placebo (P=0.02); no differences were observed from 5-24 h postoperatively. There were no significant differences between groups for visual analogue scale scores at rest, during cough, or during mobilization, pressure pain detection thresholds, von Frey hair pain detection thresholds, or peak flow. At 24 h after operation, hyperalgesia to von Frey hair stimulation proximal to the surgical wound was easily detected in 23 of 25 patients receiving dextromethorphan, and in 22 of 25 patients receiving placebo, with no significant difference between groups. Pooled data from both groups showed a weak but significant correlation between the extent of hyperalgesia at 24 h after operation, and total 24 h postoperative PCA morphine consumption (Rs=0.28, P=0.05). Three months postoperatively, hyperalgesia was still detectable in 18 of 22 examined patients in the dextromethorphan group, and in 16 of 23 patients in the placebo group, without statistical differences between groups. There were no significant differences in side-effects (nausea, vomiting, sedation). In conclusion, oral dextromethorphan 150 mg reduced PCA morphine consumption immediately (0-4 h) after hysterectomy, without prolonged effects on pain or wound hyperalgesia. A positive correlation between the magnitude of wound hyperalgesia at 24 h after operation, and total 24 h postoperative PCA morphine consumption was demonstrated.

The effect of naloxone on ketamine-induced effects on hyperalgesia and ketamine-induced side effects in humans.

BACKGROUND: The (NMDA) receptor plays a significant role in wind-up and spinal hypersensitivity and is involved in the occurrence of secondary hyperalgesia. Ketamine is an NMDA-receptor antagonist and has proven effective in alleviating secondary hyperalgesia in humans. Although it is disputed, the actions of ketamine have been ascribed not only to NMDA receptor antagonism, but also to opioid receptor agonism. A study therefore was designed in which the abolishment of a previously demonstrated effect of ketamine on secondary hyperalgesia was sought by pretreatment with naloxone. METHODS: Twenty-five volunteers were subjected to three treatment regimens. A standardized first-degree burn injury was induced. On appearance of primary and secondary hyperalgesia, one of the following infusion schemes was applied in a randomized, double-blind, cross-over fashion: (1) infusion of naloxone (0.8 mg/15 min followed by 0.4 mg/h), succeeded by infusion of ketamine (0.3 mg x kg(-1) x 15 min(-1) followed by 0.3 mg x kg(-1) x h(-1)); (2) infusion of placebo, succeeded by infusion of ketamine (0.3 mg x kg(-1) x 15 min(-1) followed by 0.3 mg x kg(-1) x h(-1)); and (3) infusion of placebo, succeeded by infusion of placebo. Heat-pain detection thresholds, magnitude of secondary hyperalgesia around the burn injury, and side effects were determined. RESULTS: Ketamine reduced secondary hyperalgesia. Naloxone did not affect the action of ketamine. The magnitudes of side effects were equal if the subjects received ketamine, regardless of preceding infusion of naloxone. CONCLUSIONS: In this experimental setting, opioid receptor blockade does not inhibit ketamine-induced reductions of secondary hyperalgesia.

Effect of preoperative extradural bupivacaine and morphine on stump sensation in lower limb amputees.

We have examined the effect of preoperative extradural bupivacaine and morphine on postoperative stump sensation in 31 patients undergoing amputation of the lower limb in a prospective, randomized, double-blind study. Patients were allocated randomly to one of two groups: group 1 received extradural 0.25% bupivacaine 4-7 ml h-1 and morphine 0.16-0.28 ml h-1 before and during operation; group 2 received extradural saline before and during amputation and conventional analgesics for pain treatment. All patients received general anaesthesia for the amputation and extradural bupivacaine and morphine after operation. Sensory examination of the limb/stump was carried out before amputation, and after 1 week and 6 months. The following were measured: pressure pain thresholds (pressure algometry), touch and pain detection thresholds (von Frey hairs), thermal sensibility (thermal rolls), and allodynia and wind-up-like pain. There were no differences between the two groups at any of the postoperative assessments for mechanical and thermal sensibility or rate of allodynia and wind-up-like pain. Our study suggests that preoperative and intraoperative extradural block had no long-term prophylactic effect on hyperalgesia, allodynia or wind-up-like pain.

Effect of i.v. ketamine in combination with epidural bupivacaine or epidural morphine on postoperative pain and wound tenderness after renal surgery.

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.

Randomised trial of epidural bupivacaine and morphine in prevention of stump and phantom pain in lower-limb amputation.

BACKGROUND: Epidural analgesia before limb amputation is commonly used to reduce postamputation pain. But there have been no controlled studies with large numbers of patients to prove such a pre-emptive effect. We investigated whether postamputation stump and phantom pain in the first year is reduced by preoperative epidural blockade with bupivacaine and morphine. METHODS: In a randomised, double-blind trial, 60 patients scheduled for lower-limb amputation were randomly assigned epidural bupivacaine (0.25% 4-7 mL/h) and morphine (0.16-0.28 mg/h) for 18 h before and during the operation (29 patients; blockade group) or epidural saline (4-7 mL/h) and oral or intramuscular morphine (31 patients; control group). All patients had general anaesthesia for the amputation and were asked about stump and phantom pain after 1 week and then after 3, 6, and 12 months by two independent examiners. Study endpoints were rate of stump and phantom pain, intensity of stump and phantom pain, and consumption of opioids. FINDINGS: Two patients in each group were withdrawn before amputation. The groups were well matched in baseline characteristics. Median duration of preoperative saline treatment was 18.5 h (IQR 17-20). Median duration of preoperative epidural blockade in the blockade group was 18 h (15-20.3). The combined median duration of postoperative epidural pain treatment in both groups was 166 h (89.3-308.3). After 1 week, 14 (52%) patients in the blockade group and 15 (56%) in the control group had phantom pain (95% CI - 30.6 to 22.7, p = 0.9). The figures for blockade versus control group were: 14 (82%) vs ten (50%; 4.0 to 60.8, p = 0.09) at 3 months; 13 (81%) vs 11 (55%; -2.7 to 55.3, p = 0.2) at 6 months; and nine (75%) vs 11 (69%; -27.0 to 39.6, p = 1.0) at 12 months. Intensity of stump and phantom pain and consumption of opioids were similar in both groups at all four postoperative interviews. INTERPRETATION: Perioperative epidural blockade started a median of 18 h (15-20.3) before the amputation and continued into the postoperative period does not prevent phantom or stump pain.

The influence of preamputation pain on postamputation stump and phantom pain.

The significance of preamputation pain for the development of postamputation stump and phantom pain has been discussed over the years and is still a matter of dispute. It has been argued that preamputation pain increases the risk of phantom pain and that phantom pain is a revivification of pain experienced before the amputation. The purpose of this prospective study was to clarify the relation between preamputation pain and phantom pain. Fifty-six patients scheduled for amputation of a lower limb were interviewed the day before the amputation about preamputation pain and about stump and phantom pain 1 week, 3 and 6 months after the amputation. Pain was quantitated and described using a visual analogue scale (VAS), 10 different word descriptors, the McGill Pain Questionnaire (MPQ) and the patients' own words. If phantom pain was present patients were asked if the pain was similar to any pain experienced before the amputation. At each postoperative interview patients were asked to recall preamputation pain intensity. Location of pain and analgesic requirements were registered. Preamputation pain significantly increased the incidence of stump pain (P = 0.04) and phantom pain (P = 0.04) after 1 week and the incidence of phantom pain after 3 months (P = 0.03). About 42% of the patients reported that their phantom pain resembled the pain they had experienced at the time of the amputation. However, there was no relation between the patients' own opinion about similarity between preamputation pain and phantom pain and the actual similarity found when comparing pre- and postoperative recordings of pain. Patients significantly overestimated preamputation pain intensity after 6 months.

Effect of systemic N-methyl-D-aspartate receptor antagonist (dextromethorphan) on primary and secondary hyperalgesia in humans.

Dextromethorphan is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist known to inhibit wind-up and central hyperexcitability of dorsal horn neurones. We studied 24 healthy, unmedicated male volunteers, aged 21-28 yr, in a randomized, double-blind, placebo-controlled, crossover study. Burn injuries were produced on the medial surface of the dominant calf with a 25 x 50 mm rectangular thermode. On three separate days, at least 1 week apart, subjects were given oral dextromethorphan 60 mg, 120 mg or placebo. Dextromethorphan reduced the magnitude of secondary hyperalgesia to pinprick but not to stroke. Dextromethorphan had no influence on primary hyperalgesia, pain during prolonged noxious heat stimulation or heat pain detection thresholds in undamaged skin. Side effects were frequent but clinically acceptable. The effects of dextromethorphan were in agreement with experimental studies indicating that dextromethorphan is a NMDA receptor antagonist. The effects of dextromethorphan in the burn injury model were similar to those of ketamine and distinct from those of local anaesthetics and opioids.

Effect of systemic N-methyl-D-aspartate receptor antagonist (ketamine) on primary and secondary hyperalgesia in humans.

Ketamine reduces nociception by binding noncompetitively to the N-methyl-D-aspartate (NMDA) receptor, activation of which increases spinal hypersensitivity. We studied 19 healthy, unmedicated male volunteers, aged 20-31 yr. Burn injuries were produced on the medial surface of the dominant calf with a 25 x 50 mm rectangular thermode. On 3 separate days, at least 1 week apart, subjects received a bolus of either ketamine 0.15 mg kg-1, ketamine 0.30 mg kg-1 or placebo, delivered by a mechanical infusion pump over 15 min. The bolus was followed by continuous infusion of ketamine 0.15 mg kg-1 h-1, ketamine 0.30 mg kg-1 h-1 or placebo, respectively, for 135 min. Ketamine reduced the magnitude of both primary and secondary hyperalgesia, and also pain evoked by prolonged noxious heat stimulation, in a dose-dependent manner. In contrast, ketamine did not alter phasic heat pain perception (perception of transient, painful, thermal stimuli) in undamaged skin. The analgesic effects of ketamine in the burn injury model are in agreement with results from experimental studies, and can be distinguished from those of local anaesthetics and opioids. Side effects caused by continuous infusion of ketamine 0.15 and 0.30 mg kg-1 h-1 were frequent but clinically acceptable.

[Cesarean section in severe double valvular disease]. / Sectio ved svaer toklapsygdom.

During pregnancy haemodynamic changes are a stress to the cardiovascular system. Women with previously asymptomatic cardiovascular disease may develop life-threatening cardiac failure because of the extra demands of pregnancy. Early diagnosis, close control and treatment during pregnancy, delivery and the postpartum period are essential. We report a case where a woman with a mitral stenosis and insufficiency of the mitral and aortic valves gave birth to a child by caesarian section.