Bent Husum

Brain oedema and blood-brain barrier permeability in pulsatile and nonpulsatile cardiopulmonary bypass

In pigs subjected to pulsatile or nonpulsatile cardiopulmonary bypass (CPB) at normothermia for 3 hours, evaluation was made of water content in brain tissue (specific gravity measurements), blood-brain permeability to serum proteins (immunocytochemical demonstration of extravasated proteins, using peroxidase-antiperoxidase technique) and histopathology (paraffin sections). The specific gravity in parietal cortex was higher after pulsatile than after nonpulsatile CPB or in control pigs, the change corresponding to a 6.3% water increase. The tissue water content was unchanged in the internal capsule, basal ganglia and nucleus accumbens after CPB. The vascular permeability to serum proteins was unchanged after nonpulsatile CPB, but after pulsatile CPB minute foci of extravasated serum proteins appeared. All the animals showed dark neurons in cortical and subcortical regions, but these could have been artefacts in immersion-fixed tissue. There were no other signs of ischaemic tissue damage. The study indicated that cortical oedema may follow pulsatile CPB, the cause being altered permeability of the blood-brain barrier to serum proteins.

Treatment with epinephrine (adrenaline) in suspected anaphylaxis during anesthesia in Denmark.

Background:Literature on the use of epinephrine in the treatment of anaphylaxis during anesthesia is very limited. The objective of this study was to investigate how often epinephrine is used in the treatment of suspected anaphylaxis during anesthesia in Denmark and whether timing of treatment is important. Methods:A retrospective study of 270 patients investigated at the Danish Anaesthesia Allergy Centre after referral due to suspected anaphylaxis during anesthesia was performed. Reactions had been graded by severity: C1, mild reactions; C2, moderate reactions; C3, anaphylactic shock with circulatory instability; C4, cardiac arrest. Use of epinephrine, dosage, route of administration, and time between onset of circulatory instability and epinephrine administration were noted. Results:A total of 122 (45.2%) of referred patients had C3 or C4 reactions; of those, 101 (82.8%) received epinephrine. Route of administration was intravenous in 95 (94%) patients. Median time from onset of reported hypotension to treatment with epinephrine was 10 min (range, 1–70 min). Defining epinephrine treatment less than or equal to 10 min after onset of hypotension as early, and more than 10 min as late, infusion was needed in 12 of 60 patients (20%) treated early versus 12 of 35 patients (34%) treated late (odds ratio, 2.09) (95% confidence interval, 0.81–5.35). Conclusion:Anaphylaxis may be difficult to diagnose during anesthesia, and treatment with epinephrine can be delayed as a consequence. Anaphylaxis should be considered and treated in patients with circulatory instability during anesthesia of no apparent cause who do not respond to the usual treatments.

Effect of General Anesthesia and Orthopedic Surgery on Serum Tryptase

Background:Mast cell tryptase is used clinically in the evaluation of anaphylaxis during anesthesia, because symptoms and signs of anaphylaxis are often masked by the effect of anesthesia. No larger studies have examined whether surgery and anesthesia affect serum tryptase. The aim of this study was to investigate the effect of anesthesia and surgery on serum tryptase in the absence of anaphylaxis. Methods:The study included 120 patients (median age, 54 yr; range, 19–94 yr) undergoing elective orthopedic surgery in general anesthesia. Exclusion criteria were allergic reactions during this or previous anesthesia, hematologic disease, or high-dose corticosteroid treatment. Blood samples for tryptase analysis (ImmunoCAP®; Phadia, Uppsala, Sweden) were drawn shortly before anesthesia and after anesthesia and surgery. Results:Median duration of anesthesia was 105 min (range, 44–263 min). Median interval between blood samples was 139 min (range, 39–370 min). Mean tryptase before surgery was 5.01 &mgr;g/l, with a mean decrease of 0.55 &mgr;g/l (P < 0.0001; 95% CI, 0.3–0.8) postoperatively. All patients received intravenous fluid (median value 750 ml; range, 200–2000 ml) perioperatively. There was no significant effect of gender, age, American Society of Anesthesiologists physical status classification, or self-reported allergy on serum tryptase. Conclusions:Serum tryptase shows small intraindividual variation in the absence of anaphylaxis. A small decrease was observed postoperatively, likely due to dilution by intravenous fluid. On suspected anaphylaxis during anesthesia, tryptase values, even within the normal reference interval, should, when possible, be compared with the patients own basal level taken more than 24 h after the reaction.

Monitoring of Sister Chromatid Exchanges in Lymphocytes of Nurse-Anesthetists

Cytogetic methods are used increasingly for monitoring exposure to potential mutagens/carcinogens in the environment. By one such method, the sister chromatid exchange (SCE) test, comparison of different groups of hospital personnel has not indicated any mutagenic effect of occupational exposure to waste anesthetic gases. Since no information is available on repeated examinations of operating room personnel during a longer period of occupational exposure, the authors examined SCE in lymphocytes in a total number of 191 venous blood samples drawn from 14 previously unexposed nurses before and during up to 32 months of training as nurse-anesthetists. The initial SCE/cell ranged from 8.03 to 13.13 SCE/cell. Individual linear regressions were performed for the transformed variable, y = (sum SCE + 1)1/2 + (sum SCE + 1)1/2, on time; and for the first 6-month period, the weighted mean of individual slopes was b0 = −0.119 ± 0.088, not significantly different from zero. Calculated for the whole observation period, b0 = 0.030 ± 0.014, P = 0.034 (two-tailed t test). Converted into SCE/cell, SCE would decrease 0.10 SCE/cell for each 6-month period of exposure (95% confidence limits 0.07–0.13 SCE/cell). The reason for this apparent decrease remains unknown. The results of the present study were in accord with previous studies of operating room personnel and of patients anesthetized with inhaled anesthetics. It was concluded that there is no indication, from the SCE test, of a mutagenic action due to exposure in vivo to currently used inhalation anesthetics.

Brain histology, blood-brain barrier and brain water after normothermic and hypothermic cardiopulmonary bypass in pigs.

The effect of hypothermia during cardiopulmonary bypass (CPB) on cerebral histopathology, blood-brain barrier permeability to serum proteins and water content was evaluated. Pigs were subjected to non-pulsatile CPB for 2 h at either normothermia or hypothermia, and a group of anaesthetised pigs served as normothermic controls. The histopathology was assessed on paraffin embedded sections. The permeability of the cerebral vessels was studied by immunocytochemical demonstration of extravasated serum proteins. The cerebral water content was assessed by specific gravity measurements. The histological studies demonstrated hydropic degeneration of the brain parenchyma and perivascular swelling of the astrocytic endfeet throughout both white and gray matter in the normothermic CPB group. Similar changes were not encountered during hypothermic CPB, which suggests a beneficial effect of decreased temperatures on brain tissue during CPB. Neither normothermic nor hypothermic CPB induced significant changes in the cerebrovascular permeability or in the specific gravities.

SCE in lymphocytes of patients treated with single, large doses of diazepam

When using the SCE test for evaluation of exposure in vivo to potential mutagens/carcinogens, it is necessary to consider possible confounding factors. In studies of possible mutagenic effects of pharmacological treatment the effect of concomitant administration of other agents such as sedatives may have to be considered. In order to assess whether diazepam per se influences SCE we have examined SCE in peripheral lymphocytes in 34 persons before and after oral administration of a single large dose of diazepam. 18 men and 16 women undergoing minor surgery of the hand received diazepam 0.2 mg kg-1 body weight orally on the day of operation, and venous blood samples were drawn on the day before the operation and again 2-5 h after the administration of diazepam. Both within cigarette smokers and non-smokers there was no statistically significant change of SCE following diazepam. It was concluded that there was no indication, from the SCE test, of an immediate mutagenic effect of a single large dose of diazepam and that such medication is not a confounding factor in studies by the SCE test.

Regional Cerebral Blood Flow and Glucose Utilization during Hypocapnia and Adenosine-induced Hypotension in the Rat

Hypocapnia and induced hypotension have been claimed by some to cause cerebral hypoxia because of insufficient perfusion. Regional cerebral blood flow (rCBF) and regional cerebral glucose utilization (rCMRglc) were measured simultaneously in the same animal subjected to hypocapnia or hypocapnia combined with induced arterial hypotension. The rCMRglc was measured with (3H) deoxyglucose and the rCBF with (14C) iodoantipyrine with the use of tissue biopsy methods and scintillation counting. Nineteen male Wistar rats were anesthetized with halothane and artificially ventilated. Anesthesia was maintained with nitrous oxide/oxygen (70:30) and succinylcholine. Six rats were maintained at normocapnia, six rats were ventilated to a PaCO2 of 20 mmHg, and seven animals were ventilated to PaCO2 20 mmHg combined with arterial hypotension of 50 mmHg (mean blood pressure) induced by infusion of adenosine. Although hypocapnia alone did not cause a statistically significant decrease of rCBF except in hippocampus, hypocapnia combined with hypotension resulted in a significant reduction of rCBF in four of seven regions when compared with hypocapnia alone; rCMRglc values were unchanged during hypocapnia. However, the addition of hypotension induced by adenosine led to a significant decline of glucose utilization in five of seven brain regions. In the present study the authors observed no increase of regional glucose utilization and hence no signs of cerebral ischemia during hypocapnia alone or combined with hypotension induced by adenosine.

Pulsatile Flow During Cardiopulmonary Bypass: Evaluation of a New Pulsatile Pump

Pulsatile cardiopulmonary bypass (CPB) has been suggested to be superior to nonpulsatile CPB. This report concerns a newly developed pulsatile pump for clinical use. It is designed as a positive displacement pump, with blood allowed to collect in a valved cavity from which it is ejected by the reciprocating action of a piston. Using a uniform procedure of anaesthesia and surgery, 14 pigs were subjected to CPB at 37 degrees C for 3 hours. The pulsatile pump was used in seven pigs and a conventional roller pump in the other seven. The wave-form of the pulse during pulsatile CPB was similar to that recorded in the pigs before bypass. The values for rate of pressure change with respect to time (dp/dt) obtained in the aorta were close to the pre-CPB values. No difference was found between the two groups with respect to platelet count or haemolysis. The investigated pulsatile device appeared to be reliable and easy to handle, and the pulsation it produced closely resembled the physiologic pulse-wave form.

Sister-chromatid exchanges in cannabis smokers

The genotoxicity of cannabis smoking was evaluated by means of the sister-chromatid exchange (SCE) test. The SCE test is considered to be a sensitive tool for the discovery of genotoxic agents in the environment. Twenty-two tobacco smokers and 22 persons smoking both tobacco and cannabis were compared. Our findings showed that smoking in itself enhanced the SCE level significantly (18.5%) compared to a group of non-smokers, but adding smoking of cannabis to tobacco smoking did not affect the SCE level further. Based on our observations cannabis smoking could not be considered genotoxic.

Hypocapnia prevents the decrease in regional cerebral metabolism during isoflurane-induced hypotension.

Summary In neurologic surgery, induced hypotension is often used while the patient is hypocapnic. We investigated, by tissue biopsy methods and scintillation counting, the regional cerebral glucose utilization (rCMRglc) and blood flow (rCBF) in rats subjected to hypocapnia alone and in combination with hypotension. Anesthesia was maintained with 1.0% isoflurane in nitrous oxide/oxygen. Seven rats were maintained at PaCO2 of 40 mm Hg, six rats were ventilated to PaCO2 of 20 mm Hg, and six animals to PaCO2 of 20 mm Hg in combination with arterial hypotension of 50 mm Hg induced by isoflurane 2.5–3.5%. During hypocapnia, rCMRglc tended to increase in all regions, but the increase was statistically insignificant; rCBF was reduced uniformly by 40%. During combined hypocapnia/hypotension, rCMRglc was unaltered when compared to hypocapnia; compared to normocapnia, increases were seen in hippocampus and cerebellum. During hypocapnia/hypotension, rCBF was unaltered in cortical areas, while increases were seen in all subcortical areas compared to hypocapnia. Regional values of the ratio of rCBF/rCMRglc indicated that during hypocapnia and hypotension induced by isoflurane in nitrous oxide/oxygen, the individual brain areas were perfused according to their metabolic needs. It is suggested that hypocapnia may prevent the decrease in rCMRglc, which is usually observed during deep isoflurane anesthesia.