Influence of local anaesthesia and local hypothermia on leucocyte, temperature, and transferrin response to surgery.

Leucocyte counts, rectal temperature, P-cortisol, P-glucose, P-transferrin, P-orosomucoid, P-IgM and hematocrit were investigated in 24 men undergoing inguinal herniotomy. The patients were randomised to epidural analgesia (n = 8), local infiltration anaesthesia (n = 8) or local infiltration anaesthesia plus local wound hypothermia with ice bags (n = 8). The rectal temperature rose (p less than 0.01) in patients randomised to epidural analgesia but not in the other groups. However, blood granulocyte and acute phase protein changes were similar in all groups. The neural blockade was sufficient in all patients as judged by lack of increase in P-cortisol and P-glucose. Thus, local infiltration anaesthesia and wound hypothermia could not prevent the inflammatory response to small clean surgery.

Dose-effect relationship of disulfiram in human volunteers. I: Clinical studies.

The aim of this study was to investigate the relation between Antabus dosage and the disulfiram-alcohol reaction (DAR) after ethanol challenge. Fifty-two healthy volunteers, 29 men and 23 women, aged 20-61 years, were treated with increasing doses of Antabuse (1, 100, 200, 300 mg) for 14 days each. At the end of each 14 days the volunteers were challenged with 0.15 g ethanol/kg body weight. Blood pressure, pulse rate, respiration rate, and symptoms such as flushing, heat sensation, nausea, vomiting, palpitations, breathlessness, and headache were monitored for the next 50 min. The volunteers left the study when they had experienced a valid DAR. A valid DAR, which was principally defined on the basis of the patients' feeling of discomfort, but for safety reasons also on the basis of unacceptable circulatory changes, was reached in 21 out of 52 volunteers after 100 mg Antabuse, in 27 after 200 mg, and in 4 after 300 mg. Most of them left the study after flushing and circulatory changes, but did not feel ill enough to be convinced that they should abstain from drinking. Ten volunteers with weak subjective symptoms, but with a valid DAR, were therefore rechallenged after the next increased dose and experienced a somewhat stronger reaction. We conclude that a daily dose of 200 mg Antabuse brings about a substantial reaction in volunteers in the presence of alcohol. The possible need for a 300 mg dose of Antabuse to prevent a patient from drinking was discussed.

Dose-effect relationship of disulfiram in human volunteers. II: A study of the relation between the disulfiram-alcohol reaction and plasma concentrations of acetaldehyde, diethyldithiocarbamic acid methyl ester, and erythrocyte aldehyde dehydrogenase activity.

The study was designed to elucidate the basic pharmacological and biochemical effects of the disulfiram dose (Antabus) provoking disulfiram-alcohol reaction (DAR) in 52 human volunteers after ethanol challenge. Disulfiram was given daily in increasing doses (1, 100, 200, and 300 mg) in successive 14 day periods, with ethanol challenge at the end of each period, until a DAR was achieved. Irrespective of dose (except the 1 mg dose), the DAR was always accompanied by almost complete inactivation (about 97%) of aldehyde dehydrogenase (ALDH) activity in erythrocytes, plasma concentrations of diethyldithiocarbamic acid methyl ester (Me-DDC) in the range of 8-472 nmol/l and accumulated plasma concentrations of acetaldehyde in the range of 7-197 mumol/l. In four of the volunteers, the cardiovascular effects of the DAR were recorded as a decrease in diastolic blood pressure (14-47 mmHg) and an increase in pulse rate (9-40 beats/min.), accompanied by a two- to fourfold increase in the plasma concentrations of adrenaline and noradrenaline. The enzyme kinetics of ALDH in erythrocytes were regularly analysed in eight volunteers during DSF intake. In addition to the expected decrease in oxidizing capacity, the Km values were also impaired, which suggests that the inhibitor is implicated in an active site directed reaction.

Effect of combined prednisolone, epidural analgesia and indomethacin on pain, systemic response and convalescence after cholecystectomy.

Twelve patients undergoing elective cholecystectomy received as analgesic medication a single dose of methylprednisolone (30 mg/kg) preoperatively and thoracic epidural analgesia with plain bupivacaine for 48 hours + epidural morphine 4 mg and systemic indomethacin 100 mg, both every 8 hours for 96 hours. Assessments of pain, various parameters of response to injury, peak flow and subjective fatigue were made preoperatively, before and 3 and 6 hours after skin incision and 1, 2, 4 and 8 days postoperatively. These patients were matched with 24 from a previous study who were treated with either intermittent nicomorphine and acetaminophen or with epidural analgesia + systemic indomethacin as analgesic medication. Preoperative methylprednisolone resulted in improved pain relief, with concomitantly reduced need for epidural bupivacaine, prevention of hyperthermic response, improved postoperative pulmonary function and lessened fatigue, while the leucocytic and acute phase responses were unmodified. There were no side effects. These results may be explained by inhibition of various trauma-induced inflammatory mediators.

Effect of patient-controlled analgesia on plasma catecholamine, cortisol and glucose concentrations after cholecystectomy.

To quantify the effects of postoperative pain relief on surgical stress response, 16 patients undergoing cholecystectomy were allocated randomly to double-blind treatment with either fentanyl by patient controlled analgesia (PCA) with the Prominject plus saline given s.c. by nurses on demand (PCA group) or saline by the infusion pump plus morphine 10 mg/70 kg s.c. by nurses on demand (control). Pain intensity (VAS) and plasma catecholamine, cortisol and glucose concentrations were measured 2-hourly for 12 h after operation. PCA improved postoperative pain intensity (P less than 0.05) and reduced plasma cortisol (P less than 0.05), but not glucose and catecholamine concentrations compared with the control group. Thus improved postoperative pain relief per se by PCA with systemic opioids had no major influence on the catabolic response to abdominal surgery.

The psychological effects of having a contact-person from the anesthetic staff.

Seventy-four patients admitted for elective surgery completed identical questionnaires and rating scales pre- and postoperatively. The course of anxiety was compared between patients who were either routinely informed or had contact with an anesthetic nurse available for support during the 30-min anesthesia and surgery preparation. Comparing the results with our three other studies, it is concluded that emotional support given by a "contact-person" is more effective than either detailed information or a tranquillizer.

Effect of alfentanil anaesthesia on the adrenocortical and hyperglycaemic response to abdominal surgery.

Plasma concentrations of cortisol and glucose were measured from before to 9 h after skin incision in 24 patients undergoing abdominal hysterectomy. The patients were randomly allocated to receive either high-dose alfentanil anaesthesia (150 micrograms kg-1 initially, followed by continuous infusion at a rate of 3 micrograms kg-1 min-1) or neurolept anaesthesia (droperidol 0.25 mg kg-1 plus fentanyl 5 micrograms kg-1 initially, followed by intermittent incremental doses of fentanyl 50 micrograms). The intraoperative and initial postoperative increases in plasma cortisol and glucose concentrations were inhibited (P less than 0.05) by alfentanil but, later in the postoperative period, both groups showed identical increases in cortisol and glucose concentrations. Mean arterial pressure and heart rate were more stable in the alfentanil group. The concept of "stress-free" anaesthesia during high-dose opiate administration seems to be valid during operation and for the initial 1-3 h into the postoperative period.

Subarachnoid anaesthesia with 0.5% bupivacaine: effects of density.

The effects of subarachnoid administration of 0.5% bupivacaine 4 ml in 8%, 5% or 0% glucose were investigated in a double-blind study in 30 women undergoing laparotomy through a lower abdominal incision. The onset time for maximum segmental spread of analgesia was 10-15 min for all solutions. Cephalad segmental spread of analgesia was three to four segments higher with the hyperbaric solutions (T4-5 v. T7-8). Time of onset of complete motor blockade of the lower limbs was 5-10 min for all solutions. The glucose-free solution did not produce sufficient surgical anaesthesia because of too low cephalad spread. Duration of motor blockade generally decreased with increasing glucose concentration, only the hyperbaric solutions providing useful for abdominal surgery, with a duration of 1-1.5 h. Anaesthesia (halothane) was required in seven of 10 patients in the glucose-free group and in five of 20 in the hyperbaric groups. No occurrence of "post-spinal headache" was recorded in the study.

The modifying effect of spinal anaesthesia on intra- and postoperative adrenocortical and hyperglycaemic response to surgery.

Plasma cortisol and glucose were measured in 24 patients undergoing abdominal hysterectomy during spinal anaesthesia with 0.5% hyperbaric tetracaine or neurolept anaesthesia. The sensory level of analgesia to pinprick extended to at least T4 before skin incision in the spinal group. The mean sensory analgesic level regressed almost linearly, reaching the fourth lumbar segment 4 h after incision. Plasma cortisol and glucose measurements from before to 9 h after skin incision showed significant increases in both parameters during and after surgery. Plasma cortisol and glucose levels were significantly lower during and immediately after surgery in the spinal group, but later postoperatively the mean levels were similar in the two groups. The increase in plasma cortisol 1 h after skin incision in the spinal group correlated to the segmental level of analgesia at that time (r = 0.77, P less than 0.01) and a similar correlation was found with regard to plasma glucose changes (r = 0.60, P less than 0.05). The regression lines showed that maintenance of a sensory analgesic level about the fourth thoracic segment prevented the adrenocortical and hyperglycaemic response to surgery. These findings are in accordance with the anatomical assumption that the upper segmental level of visceral afferent input to the spinal cord is about the fourth thoracic segment. Our results further demonstrate that the inhibitory effect of spinal anaesthesia on the stress response to surgery is transient, and correlates to the regression of sensory analgesia.

Bronchopleural leakage treated with fibrin sealant and high-frequency positive-pressure ventilation.

In a 62-year-old man, left spontaneous pneumothorax appeared 14 days after right pneumonectomy. The large air leakage necessitated thoracotomy and resection of a bullous area in the left upper lobe. Pleurectomy was not performed. The air leakage continued for 14 more days until, at a second left thoracotomy, numerous bullae were oversewn and covered with fibrin sealant. High-frequency positive-pressure ventilation (90 respirations/min, 21 l/min) was used for the following 6 hours. After 18 hours there was no more air leakage during spontaneous ventilation and the patient made a good recovery.

Pain treatment on outpatient basis utilizing extradural opiates. A Danish multicentre study comprising 105 patients.

Previous to October 1st, 1981, 8 major Danish anaesthesiological departments registered 105 patients treated with extradural opiates for a period of more than 7 days, partially or completely on outpatient basis. Ninety-four suffered from painful malignant diseases and 11 patients from various painful benign diseases. The mean period of treatment was 65 days (range: 7-283 days) and of these 49 days (2-266 days) as outpatients. The total number of inserted epidural catheters was 215, equivalent of an average of 2 per patient (range 1-5). Reasons for removing an extradural catheter were injection-related pain, difficulty in injecting the desired volume, and displacement of catheter. Morphine chloride, in a solution of 0.4 mg/ml of normal saline, was the main choice as analgesic agent (90 patients). The mean daily dose of this drug totalled 12.6 +/- 4.8 mg (S.D.) (range: 4-30 mg) distributed as 2.7 +/- 0.9 (S.D.) (range: 1-6) daily injections. Twelve patients were treated with buprenorphine extradurally. Satisfactory pain relief was achieved for 70 patients (67%) who managed with extradural opiates as sole analgesic treatment. One patient developed septicaemia with a non-fatal outcome probably originating from some other focus. Apart from this no serious side effects were reported. Medically unskilled persons or relatives were responsible for instillation of all extradural opiates with 42 patients and partially responsible with 14 patients. Eleven patients managed injections without assistance. District nurses took care of medication for 46 patients, aided by a general practitioner in 5 cases. Three patients were supplied with continuous extradural infusion by means of a Mill Hill microinfusion pump.

Respiratory depression and morphine concentration in serum after epidural and intramuscular administration of morphine.

The ventilatory response to carbon dioxide and the serum level of free morphine were measured in six adult patients scheduled for operation under lumbar epidural analgesia. The investigation was performed on 2 consecutive days before the operation. The measurements were performed before, and 30 and 90 min after the intramuscular administration of morphine chloride (0.15 mg/kg body weight) as well as lumbar epidural administration of morphine chloride (5 mg morphine chloride diluted in 10 ml isotonic saline). The ventilatory response to carbon dioxide was depressed significantly both 30 and 90 min after epidurally administered morphine compared to the control value, while the depression of the ventilatory response was demonstrated in only five of six patients 30 min after intramuscularly administered morphine. The peak serum levels of free morphine were reached within 20 min of administration and it seemed that the injected quantity of morphine and not the method of administration determined the serum level.

Epidural morphine for postoperative pain relief.

In a clinical, double-blind study including 45 patients, who all underwent lower abdominal or urological surgery, the analgesic effect, latency and duration of epidural application of morphine were investigated in doses of 2 and 4 mg, respectively, compared to placebo. No significant difference was found in the effect of 2 mg morphine, compared to placebo. A significant decrease in pain score was found in the group of patients who received 4 mg morphine administered epidurally; however, this effect did not occur until 60 min after epidural administration. The effect of 4 mg morphine was found to be of long duration, as eight out of 15 patients did not require any supplementary analgesics within the first 24 h, compared to two out of 14 and three out of 15 patients, respectively, in the placebo and 2-mg groups.

Influence of epidural analgesia on postoperative changes in various serum enzyme patterns and serum bilirubin.

Postoperative changes in serum bilirubin, various serum enzymes (alanine-amino transferase ALAT), alkaline phosphatase (AP), lactate-dehydrogenase (LDH), and creatine-phosphokinase (CPK)), plasma glucose and cortisol were studied in 20 healthy, premenopausal women undergoing elective abdominal hysterectomy under either general anaesthesia with halothane or epidural analgesia (T4-S5). Surgery under general anaesthesia was followed by increased levels of bilirubin, LDH, CPK, glucose and cortisol, whereas AP and ALAT were unaffected by surgery. Epidural analgesia inhibited increases in LDH, CPK, glucose and cortisol (P less than 0.05), but not the increase in bilirubin. The results indicate that afferent neurogenic stimuli from the surgical area are important in mediating the postoperative changes in LDH and CPK, whereas factors other than neurogenic stimuli or adrenal hormones are responsible for the postoperative changes in bilirubin.

The iliac vein compression syndrome. A case report with a review of the literature.

The iliac compression syndrome results from reduced venous return from the left leg due to pressure from the right common iliac artery on the underlying left common iliac vein where it enters the inferior vena cava. The pressure results in intravenous band and adhesion formation which can lead to iliofemoral thrombosis with insufficient recanalization. We present such a case in a young man who had swelling, venous claudication, siderosclerosis, and skin ulcers. The syndrome was diagnosed by pelvic phlebography, arteriography, venous emptying time, and venous pressure measurement. Palma's crossover operation was performed, in which the contralateral great saphenous vein was transposed subcutaneously to the ipsilateral common femoral vein peripheral to the obstruction. To avoid graft thrombosis, a temporary arterio-venous fistula was created. Follow-up six months after the operation showed the operative result to the satisfactory.

Anxiety and sedation during a stressful situation after single dose of diazepam versus N-desmethyldiazepam--a controlled trial.

Twenty milligram diazepam (DZ) was compared with 20 mg of its main metabolite N-desmethyldiazepam (NDDZ) as single dose, oral premedication in a genuine stressful situation. Fifty patients participated in the randomized, double-blind controlled study. Anxiety and sedation were measured the day before an operation and one hour after premedication, just before the operation. NDDZ was significantly less sedative while the degree of anxiety was rated equal in the two groups. The results may support the hypothesis that a competition between DZ and NDDZ can explain the shift in the effect profile of DZ during long term treatment.