Niels Vidiendal Olsen

Consensus Meeting on Microdialysis in Neurointensive Care

BackgroundMicrodialysis is used in many European neurointensive care units to monitor brain chemistry in patients suffering subarachnoid hemorrhage (SAH) or traumatic brain injury (TBI).DiscussionWe present a consensus agreement achieved at a meeting in Stockholm by a group of experienced users of microdialysis in neurointensive care, defining the use of microdialysis, placement of catheters, unreliable values, chemical markers, and clinical use in SAH and in TBI.ConclusionsAs microdialysis is maturing into a clinically useful technique for early detection of cerebral ischemia and secondary brain damage, there is a need to following such definition regarding when and how to use microdialysis after SAH and TBI.

Acute hypoxia and hypoxic exercise induce DNA strand breaks and oxidative DNA damage in humans

The present study investigated the effect of a single bout of exhaustive exercise on the generation of DNA strand breaks and oxidative DNA damage under normal conditions and at high‐altitude hypoxia (4559 meters for 3 days). Twelve healthy subjects performed a maximal bicycle exercise test; lymphocytes were isolated for analysis of DNA strand breaks and oxidatively altered nucleotides, detected by endonuclease III and formamidipyridine glycosylase (FPG) enzymes. Urine was collected for 24 h periods for analysis of 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine (8‐oxodG), a marker of oxidative DNA damage. Urinary excretion of 8‐oxodG increased during the first day in altitude hypoxia, and there were more endonuclease III‐sensitive sites on day 3 at high altitude. The subjects had more DNA strand breaks in altitude hypoxia than at sea level. The level of DNA strand breaks further increased immediately after exercise in altitude hypoxia. Exercise‐induced generation of DNA strand breaks was not seen at sea level. In both environments, the level of FPG and endonuclease III‐sensitive sites remained unchanged immediately after exercise. DNA strand breaks and oxidative DNAdamage are probably produced by reactive oxygen species, generated by leakage of the mitochondrial respiration or during a hypoxia‐induced inflammation. Furthermore, the presence of DNA strand breaks may play an important role in maintaining hypoxia‐induced inflammation processes. Hypoxia seems to deplete the antioxidant system of its capacity to withstand oxidative stress produced by exhaustive exercise.—Møller, P., Loft, S., Lundby, C., Olsen, N. V. Acute hypoxia and hypoxic exercise induce DNAstrand breaks and oxidative DNA damage in humans. FASEB J. 15, 1181–1186 (2001)

The effect of altitude hypoxia on glucose homeostasis in men

1 Exposure to altitude hypoxia elicits changes in glucose homeostasis with increases in glucose and insulin concentrations within the first few days at altitude. Both increased and unchanged hepatic glucose production (HGP) have previously been reported in response to acute altitude hypoxia. Insulin action on glucose uptake has never been investigated during altitude hypoxia. 2 In eight healthy, sea level resident men (27 ± 1 years (mean ± S.E.M.); weight, 72 ± 2 kg; height, 182 ± 2 cm) hyperinsulinaemic (50 mU min−1 m−2), euglycaemic clamps were carried out at sea level, and subsequently on days 2 and 7 after a rapid passive ascent to an altitude of 4559 m. 3 Acute mountain sickness scores increased in the first days of altitude exposure, with a peak on day 2. Basal HGP did not change with the transition from sea level (2.2 ± 0.2 mg min− kg−1) to altitude (2.0 ± 0.1 and 2.1 ± 0.2 mg min−1 kg−1, days 2 and 7, respectively). Insulin‐stimulated glucose uptake rate was halved on day two compared with sea level (4.5 ± 0.6 and 9.8 ± 1.1 mg min−1 kg−1, respectively; P < 0.05), and was partly restored on day 7 (7.4 ± 1.4 mg min−1 kg−1; P < 0.05vs. day two and sea level). Concentrations of glucagon and growth hormone remained unchanged, whereas glucose, C‐peptide and cortisol increased on day 2. Noradrenaline concentrations increased during the stay at altitude, while adrenaline concentrations remained unchanged. In response to insulin infusion, catecholamines increased on day 2 (noradrenaline and adrenaline) and day 7 (adrenaline), but not at sea level. 4 In conclusion, insulin action decreases markedly in response to two days of altitude hypoxia, but improves with more prolonged exposure. HGP is always unchanged. The changes in insulin action may in part be explained by the changes in counter‐regulatory hormones.

Manual evaluation of residual curarization using double burst stimulation: a comparison with train-of-four

Double burst stimulation (DBS) is a new mode of stimulation developed to reveal residual neuromuscular blockade under clinical conditions. The stimulus consists of two short bursts of 50 Hz tetanic stimulation, separated by 750 ms, and the response to the stimulation is two short muscle contractions. Fade in the response results from neuromuscular blockade as with train-of-four stimulation (TOF). The authors compared the sensitivity of DBS and TOF in the detection of residual neuromuscular blockade during clinical anaesthesia. Fifty-two healthy patients undergoing surgery were studied. For both stimulation patterns the frequencies of manually detectable fade in the response to stimulation were determined and compared at various electromechanically measured TOF ratios. A total of 369 fade evaluations for DBS and TOF were performed. Fade frequencies were statistically significantly higher with DBS than with TOF, regardless of the TOF ratio level. Absence of fade with TOF implied a 48% chance of considerable residual relaxation as compared with 9% when fade was absent with DBS. The results demonstrate that DBS is more sensitive than TOF in the manual detection of residual neuromuscular blockade.

Comparison of cardiac output measurement techniques: thermodilution, Doppler, GO2‐rebreathing and the direct Fick method

Simultaneously measured cardiac output obtained by thermodilution (TD), transcutaneous suprasternal ultrasonic Doppler (DOP), CO2‐rebreatliing (CR) and the direct Fick method (FI) were compared in eleven healthy subjects in a supine position (SU), a sitting position (SI), and during sitting exercise at a workload of 50 W (EX). The agreements between the techniques, two by two, were expressed as the bias calculated as the averaged differences between the techniques. Precision was expressed as the standard deviation of the bias. The overall agreement (bias±precision) between TD, DOP and CR respectively and FI were 2.3±1.6. ‐0.1 ±1.4, and ‐0.2±1.1 1/min. TD overestimated cardiac output consistently in SU, SI and EX. DOP was in‐accurate during EX and agreed well with FI in SU and SI. CR agreed closely with FI in SI and EX, but values were underestimated in SU. The overall agreement between DOP and CR, respectively, and TD were 2.5±2.2 and 2.6±1.6 1/min. The overall agreement between DOP and CR was 0.1 ± 1.6 1/min. In conclusion, TD overestimated cardiac output compared to the other techniques and the poor agreement has to be taken into consideration especially in measures of low values. The precision of DOP and CR against FI seems to be within clinically acceptable limits, and these methods may provide interchangeable alternatives to the invasive Fick method.

Hypoxemia increases serum interleukin-6 in humans

Abstract Serum concentrations of interleukin (IL) 1 beta, IL-1 receptor antagonist (IL-1ra), IL-6, tumor necrosis factor (TNF) alpha, and C-reactive protein (CRP) were determined in ten healthy men at sea level and during four days of altitude hypoxia (4350m above sea level). The mean (SD) arterial blood oxygen saturations were 78.6 (7.3)%, 82.4 (4.9)%, and 83.4 (5.3)% in the first, second, and third days at altitude, respectively. A symptom score of acute mountain sickness (AMS) revealed that the subjects had mostly light symptoms of AMS. Mean serum IL-6 increased from 1.36 (1.04) pg × ml–1 at sea level to 3.10 (1.65), 4.71 (2.81), and 3,54 (2.17) pg × ml–1 during the first three days at altitude, and to 9.96 (8.90) pg × ml–1 on the fourth day at altitude (ANOVA p =0.002). No changes occurred in serum concentrations of IL-1 beta, IL-1ra, TNF alpha, or CRP. The serum IL-6 were related to SaO2, ( r =–0.45, p =0.003), but not to heart rates or AMS scores. In conclusion, human serum concentrations of IL-6 increased during altitude hypoxia whereas the other proinflammatory cytokines remained unchanged. The major role of IL-6 during altitude hypoxia seem not to be mediation of inflammation, instead, the role of IL-6 could be to stimulate the erythropoiesis at altitude.

A single subcutaneous bolus of erythropoietin normalizes cerebral blood flow autoregulation after subarachnoid haemorrhage in rats

Systemic administration of recombinant erythropoietin (EPO) has been demonstrated to mediate neuroprotection. This effect of EPO may in part rely on a beneficial effect on cerebrovascular dysfunction leading to ischaemic neuronal damage. We investigated the in vivo effects of subcutaneously administered recombinant EPO on impaired cerebral blood flow (CBF) autoregulation after experimental subarachnoid haemorrhage (SAH). Four groups of male Sprague‐Dawley rats were studied: group A, sham operation plus vehicle; group B, sham operation plus EPO; group C, SAH plus vehicle; group D, SAH plus EPO. SAH was induced by injection of 0.07 ml of autologous blood into the cisterna magna. EPO (400 iu kg−1 s.c.) or vehicle was given immediately after the subarachnoid injection of blood or saline. Forty‐eight hours after the induction of SAH, CBF autoregulatory function was evaluated using the intracarotid 133Xe method. CBF autoregulation was preserved in both sham‐operated groups (lower limits of mean arterial blood pressure: 91±3 and 98±3 mmHg in groups A and B, respectively). In the vehicle treated SAH‐group, autoregulation was abolished and the relationship between CBF and blood pressure was best described by a single linear regression line. A subcutaneous injection of EPO given immediately after the induction of SAH normalized autoregulation of CBF (lower limit in group D: 93±4 mmHg, NS compared with groups A and B). Early activation of endothelial EPO receptors may represent a potential therapeutic strategy in the treatment of cerebrovascular perturbations after SAH.

“Live high–train low” using normobaric hypoxia: a double-blinded, placebo-controlled study

The combination of living at altitude and training near sea level [live high-train low (LHTL)] may improve performance of endurance athletes. However, to date, no study can rule out a potential placebo effect as at least part of the explanation, especially for performance measures. With the use of a placebo-controlled, double-blinded design, we tested the hypothesis that LHTL-related improvements in endurance performance are mediated through physiological mechanisms and not through a placebo effect. Sixteen endurance cyclists trained for 8 wk at low altitude (<1,200 m). After a 2-wk lead-in period, athletes spent 16 h/day for the following 4 wk in rooms flushed with either normal air (placebo group, n = 6) or normobaric hypoxia, corresponding to an altitude of 3,000 m (LHTL group, n = 10). Physiological investigations were performed twice during the lead-in period, after 3 and 4 wk during the LHTL intervention, and again, 1 and 2 wk after the LHTL intervention. Questionnaires revealed that subjects were unaware of group classification. Weekly training effort was similar between groups. Hb mass, maximal oxygen uptake (VO(2)) in normoxia, and at a simulated altitude of 2,500 m and mean power output in a simulated, 26.15-km time trial remained unchanged in both groups throughout the study. Exercise economy (i.e., VO(2) measured at 200 W) did not change during the LHTL intervention and was never significantly different between groups. In conclusion, 4 wk of LHTL, using 16 h/day of normobaric hypoxia, did not improve endurance performance or any of the measured, associated physiological variables.

Does perioperative tactile evaluation of the train-of-four response influence the frequency of postoperative residual neuromuscular blockade?

The authors conducted a randomized controlled clinical trial to evaluate the usefulness of perioperative manual evaluation of the response to train-of-four (TOF) nerve stimulation. A total of 80 patients were divided into four groups of 20 each. For two groups (one given vecuronium and one pancuronium), the anesthetists assessed the degree of neuromuscular blockade during operation and during recovery from neuromuscular blockade by manual evaluation of the response to TOF nerve stimulation. In the other two groups, one of which received vecuronium and the other pancuronium, the anesthetists evaluated the degree of neuromuscular blockade solely by clinical criteria. The use of a nerve stimulator was found to have no effect on the dose of relaxant given during anesthesia, on the need for supplementary doses of anticholinesterase in the recovery room, on the time from end of surgery to end of anesthesia, or on the incidence of postoperative residual neuromuscular blockade evaluated clinically. The median (and range of) TOF ratios recorded in the recovery room were 0.75 (0.33-0.96) and 0.79 (0.10-0.97) in the vecuronium groups monitored with and without a nerve stimulator, respectively. These ratios were significantly higher than those found in the pancuronium groups, which wre 0.66 (0.06-0.90) and 0.63 (0.29-0.95), respectively. However, no difference was found between the vecuronium and pancuronium groups in the number of patients showing clinical signs of residual neuromuscular blockade, as evaluated by the 5-s head-lift test.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence of primary Raynaud phenomena in young females

A questionnaire concerning Raynauds phenomenon was sent to eighty-five females (aged 21--50 years) working as physical therapists at municipal hospitals in Copenhagen. Fifteen of sixty-seven healthy young females (22%, 95% confidence limits 13--34%) were classified as having Raynaud phenomena in its primary form. Twenty-four persons underwent a detailed clinical investigation with measurement of blood pressure at the arm and fingers with cuff techniques. Cold provocation test on one finger was carried out after moderate body cooling. Of eight subjects being classified from the questionnaire as having Raynaud phenomena, six showed closure of the digital arteries at the local cold provocation, and all had an exaggerated response. A group complaining of cold fingers showed a greater reduction in finger blood pressure during local cooling than the normal group, but none showed closure. A questionnaire can separate the groups if Raynaud phenomena is defined by appearance of white and dead fingers on cold exposure with frequent cold or bluish fingers.