[Strategy of ulcer therapy--should the debate forum be in the court or office?].
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Biomedical subjects
Publications and source records attributed to H Kehlet.
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Retrospective studies suggest increased postoperative morbidity among alcohol misusers. We have prospectively studied the risk associated with alcohol intake among patients undergoing surgery. We investigated 15 persons who required colorectal surgery and who were drinking at least five Danish drinks per day. These patients were matched for sex, nutrition, age, weight, cardio-pulmonary disease, diagnosis anesthesia, and surgery to 15 control persons who were consuming no more than two drinks daily. None of the patients showed signs of liver disease. The alcohol group developed more postoperative complications than controls (67 vs 20%, p < 0.05) and hospital stay was prolonged (20 vs 12 days, p < 0.05). Preoperatively, alcohol misusers had reduced left ventricular ejection fraction (54 vs 68%, p < 0.01). Delayed-type hypersensitivity responses were reduced in the alcohol group before (53 mm2 vs 78, p < 0.05) and after (18 mm2 vs 55, p < 0.01) surgery. Alcohol misusers had significantly longer bleeding times. Surgical stress responses, as assessed by changes in plasma cortisol and catecholamines, were higher among alcohol misusers (p < 0.05). Postoperative morbidity was increased in alcohol misusers without signs of liver damage. The mechanisms may include subclinical cardiac insufficiency, immunosuppression, and decreased haemostatic function. Preoperative alcohol consumption may be a more important risk factor for postoperative morbidity than previously thought.
The effect of oxygen therapy (37% by face mask) and epidural local anesthetic blockade (9 ml 0.5% bupivacaine at Th9-11 level) on wound oxygenation was evaluated in eight otherwise healthy patients undergoing elective colorectal resection. The patients were monitored continuously for subcutaneous oxygen tension, arterial oxygen saturation, heart rate, and skin temperature on the day after operation, and arterial blood for gas analysis was drawn every 15 min during the study. A fluid challenge (10 ml saline/kg body wt) did not alter any of the measured values. The epidural blockade did not change any of the measured values. Oxygen therapy before epidural blockade increased median subcutaneous oxygen tension from 60 to 71 mmHg (P < 0.02) and, after epidural blockade, from 64 to 71 mmHg (P < 0.02) Time to reach steady state in subcutaneous oxygen tension with oxygen therapy was 30 (15-55) min without epidural blockade and 15 (10-20) min with blockade (P < 0.03). In conclusion, epidural local anesthetic blockade did not increase subcutaneous oxygen tension with or without oxygen therapy after elective uncomplicated major abdominal surgery.
This study investigated the antinociceptive and anti-inflammatory effect of a topical non-steroidal anti-inflammatory drug in human thermal injury. Twelve healthy unmedicated volunteers had identical burn injuries produced on the medial side of both calves with a 49 degrees C 15 x 25 mm thermode. Ketorolac gel or placebo were randomly applied on the right or left calf 1.5 h before burn injury, immediately after burn injury and 6 and 12 h later in a double-blind trial where every subject served as his own control. Heat pain detection thresholds (HPDT), head pain tolerance (HPT), mechanical pain detection thresholds (MPDT) and the intensity of burn-induced erythema (erythema index, EI) were assessed in the area of the thermal injury, and areas of hyperalgesia to pin prick were determined outside the injury before and 3, 6 and 24 h after the burn injury. Burn injury led to a decrease in HPDT, HPT and MPDT, an increase in EI and development of mechanical hyperalgesia (P < 0.05). Ketorolac gel had no effect on any of the nociceptive or inflammatory variables studies (P > 0.2).
Ten patients undergoing major abdominal surgery under general anaesthesia were monitored with a pulse oximeter, electroencephalogram, electromyogram, electrocardiogram and eye and hand movement sensors two nights before and three nights after surgery. Episodic hypoxaemic events were increased significantly after surgery (P < 0.05). Rapid eye movement (REM) sleep decreased significantly on the first night after operation (P < 0.05). Seven patients had increased amounts of REM sleep (rebound) on the second, third or both nights after operation compared with the preoperative night. Slow wave sleep was depressed significantly on the first two nights after operation (P < 0.05). REM sleep-associated hypoxaemic episodes for individual patients increased about three-fold on the second and third nights after operation compared with the night before operation (P < 0.05). We conclude that postoperative sleep pattern is disturbed severely with early depression of REM and slow wave sleep and with rebound of REM sleep on the second and third nights. Postoperative rebound of REM sleep may contribute to the development of sleep disordered breathing and nocturnal episodic hypoxaemia.
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We have studied the antinociceptive and anti-inflammatory effects of topical glucocorticoids in human thermal injury. The right and left legs of 12 healthy volunteers were allocated randomly to be treated with either 0.05% clobetasol propionate cream or placebo in a double-blind trial. Thermal injuries were induced with a thermode, which was heated to 49 degrees C for 5 min under standardized pressure. Clobetasol propionate or placebo cream was applied to the skin 1 h before burn injury, immediately after the injury and every 12 h for the next 3 days. Heat pain detection thresholds (HPDT), heat pain tolerance (HPT), mechanical pain detection thresholds (MPDT) and the intensity of burn-induced erythema (erythema index, EI) were assessed inside the thermal injury and areas of hyperalgesia to pinprick outside the injury were determined before and regularly for 72 h after the burn injury. Burn injury caused a decrease in HPDT, HPT and MPDT, an increase in EI and development of mechanical, secondary hyperalgesia. Clobetasol propionate had no effect on any of the nociceptive or inflammatory variables studied.
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Forty-two patients scheduled for total knee arthroplasty (n = 20) or hip arthroplasty (n = 22) were randomly allocated to receive either continuous epidural bupivacaine/morphine for 48 h postoperatively plus oral piroxicam, or general anaesthesia followed by a conventional intramuscular opioid and acetaminophen regimen. Patients undergoing knee- or hip arthroplasty treated with epidural analgesia had significantly lower pain scores during mobilization under the 48 h epidural infusion compared with patients receiving conventional treatment, while no important differences were observed after cessation of the epidural regimen. However, the achieved pain relief had no impact on postoperative convalescence parameters, such as ambulation, patient activity including need for nursing care, fatigue or hospital stay. Late postoperative pain, fatigue and conservative attitudes and routines in the postoperative care, were the most important reasons limiting mobilization and activity. We conclude that effective early (48 h) postoperative pain relief with balanced analgesia does not per se lead to important improvements in convalescence and hospital stay.
Thirty-two patients scheduled for total knee arthroplasty were randomized to receive an identical epidural blockade initiated 30 min before surgical incision (N = 16), or at closure of the surgical wound (N = 16). Before induction of general anaesthesia the epidural catheter was tested with bupivacaine 7.5 mg.ml-1, 2 ml. General anaesthesia was induced with thiopentone, pancuronium or atracurium, and fentanyl 0.1-0.3 mg, and maintained with N2O/O2 and enflurane. The epidural regimen consisted of a bolus of 16 ml of bupivacaine 7.5 mg.ml-1 plus morphine 2 mg, and continuous infusion of bupivacaine 1.25 mg.ml-1 plus morphine 0.05 mg.ml-1, 4 ml.h-1 for the first 24 h, and bupivacaine 0.625 mg.ml-1 plus morphine 0.05 mg.ml-1, 4 ml.h-1, for the next 24 h after operation. Additional morphine 2.5-5 mg was administered i.v. or i.m. for the first 24 h postoperatively, and ketobemidone or morphine 5-10 mg orally or rectally from 24 h to 7 d postoperatively, on request. Paracetamol 1000 mg every 8 h was administered from 48 h to 7 days postoperatively. No significant differences were observed in request for additional opioids, or in pain scores at rest or during mobilisation of the operated limb, during or after cessation of the epidural regimen. These results do not suggest timing of analgesia with a conventional, continuous epidural regimen to be of major clinical importance in patients undergoing total knee arthroplasty.
Seventy-two patients with acute cholecystitis were treated with initial ultrasound-guided percutaneous transperitoneal cholecystostomy (PTCS). PTCS could be performed in all 72 patients almost without procedure related complications, and subsequent elective treatment could be done in all, except three patients where acute cholecystectomy was necessary because of accidental catheter dislocation. Seven patients died of their severe underlying illness without relationship to PTCS or cholecystitis. Eight patients with acalculous cholecystitis had no further treatment after removal of the drainage catheter. It is concluded that PTCS is a safe method for acute drainage in patients with acute cholecystitis.
Medical treatment of peptic ulcer disease with H2-blockers has over the last ten years practically replaced surgical treatment of this condition, due to greater patient compliance, high effectivity and negligible side-effects. The treatment is, however, strained by the relatively high cost of medication. Development of techniques for laparoscopic vagotomy, which is associated with a considerably reduced postoperative morbidity and reconvalescence as well as entailing only one to two days hospitalization and a minimal surgical scar, has re-opened the debate on medical versus surgical treatment of ulcers. On the basis of a literature review of risk of ulcer recurrence, risk of ulcer complications, cost and compliance associated with the two types of treatment, it is concluded that surgical treatment of peptic ulcers by laparoscopic parietal cell vagotomy should have a renaissance as regards the treatment of patients, who have frequent recurrences when maintained on ordinary medical treatment. However, the development of new, alternative principles for the cheap, effective and complication-free medical treatment of these patients, for example via elimination of helicobacter pylori infection, will necessitate a re-evaluation as regards the treatment of choice.
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We have examined the time course of, and relationship between, primary and secondary hyperalgesia after thermal injury to the skin in humans. Burn injuries (15 x 25 mm rectangular thermode, 49 degrees C, 5 min) were produced in eight healthy, unmedicated male volunteers, on the medial side of the right calf, on two occasions at least 8 days apart. Heat pain detection thresholds (HPDT), heat pain tolerance (HPT), mechanical pain detection threshold (MPDT) and the intensity of burn-injury induced erythema (skin erythema index, SEI) were assessed inside the burn injury. HPT was assessed only in one study period. Areas of hyperalgesia to pinprick and brush were determined outside the injury. Assessments were made before and regularly for 72 h after the burn injury. There was a decrease in heat pain and mechanical thresholds, an increase in SEI inside the injury and development of mechanical hyperalgesia outside the injury. These alterations were consistent between the two examination days. The time course of the intensity of primary hyperalgesia was related closely to that of changes in area of secondary hyperalgesia, and hyperalgesia outside the injury did not outlast hyperalgesia inside the injury in any volunteer. These findings suggest post-injury development of secondary hyperalgesia to be a dynamic process, closely related in time to a peripheral nociceptive input, with reversal to normal when the peripheral lesion disappears. These observations may be relevant to the concept of "pre-emptive" analgesia.
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