To improve heat transfer, the Medivance Arctic Sun® Temperature Management System (Medivance, Inc., Louisville, CO, USA) features an adhesive, water-conditioned, highly conductive hydrogel pad for intimate skin contact. This study measured and compared the heat transfer coefficient (h), i.e. heat transfer efficiency, of this pad (hPAD), in a heated model and in nine volunteers’ thighs; and of 10°C water (hWATER) in 33 head-out immersions by 11 volunteers.

Volunteer studies had ethical approval and written informed consent. Calibrated heat flux transducers measured heat flux (W m−2). Temperature gradient (ΔT) was measured between skin and pad or water temperatures. Temperature gradient was changed through the pad’s water temperature controller or by skin cooling on immersion.

The heat transfer coefficient is the slope of W m−2/ΔT: its unit is W m−2 °C−1. Average with (95% CI) was: model, hPAD = 110.4 (107.8–113.1), R2 = 0.99, n = 45; volunteers, hPAD = 109.8 (95.5–124.1), R2 = 0.83, n = 51; and water immersion, hWATER = 107.1 (98.1–116), R2 = 0.86, n = 94.

The heat transfer coefficient for the pad was the same in the model and volunteers, and equivalent to hWATER. Therefore, for the same ΔT and heat transfer area, the Arctic Sun’s heat transfer rate would equal water immersion. This has important implications for body cooling/rewarming rates.

Radical prostatectomy is at high risk for intraoperative and postoperative bleeding due to surgical trauma, release of urokinase and tissue type plasminogen activator. We conducted this prospective, observational multi-centre study to assess the degree of systemic fibrinolysis or hypercoagulation in the perioperative period. We studied serial changes in standard laboratory values and in thrombelastographic (TEG®; Haemoscope Corporation, Skokie, IL, USA) parameters including lysis at 30 and 60 min (LY-30, LY-60), alpha-angle (α) and maximum amplitude.

In all, 49 patients undergoing radical retropubic prostatectomy in five Italian University Hospitals were included. Blood samples were taken before surgery (T1), at the removal of the prostate (T2), 4 h after surgery (T3) and then 1 day after surgery (T4). Native blood samples were analysed using a thrombelastograph Haemoscope 5000 (Haemoscope Corporation).

We did not see any relevant activation of fibrinolysis during any stage. Intraoperatively, we showed even more activated blood coagulation with consumption of fibrinogen and a reduced TEG® percentage clot lysis. Only at the first postoperative sample point we saw a trend towards a more fibrinolytic state indicated by increasing partial thromboplastin time, LY-30 and LY-60 values, and a peak of the fibrin degradation product D-dimers. This is consistent with a normal reaction to the hypercoagulable state before and is unlikely to be due to an intraoperative tissue type plasminogen activator release. We found no evidence of an uncontrolled activation of fibrinolysis on the day after surgery. On the contrary, α-values which indicate the rate of clot formation and which increase during hypercoagulation showed the tendency to rise slightly compared with the preoperative value.

Neither standard coagulation parameters nor TEG® values showed any significant activation of fibrinolysis or of hypercoagulation in the preoperative period. Nevertheless, hypercoagulation seems to have a substantial clinical impact as it has been shown that cardiovascular complications and pulmonary embolism were the most common causes of death after retropubic prostatectomy.

Adrenomedullin is a potent vasodilatory peptide. The mechanisms of adrenomedullin-induced responses are via guanine nucleotide guanosine 5′-triphosphate-binding protein (G-protein)-coupled receptor activation and are similar to those of calcitonin gene-related peptide (CGRP). Previously, we reported that sevoflurane and isoflurane inhibit CGRP-induced haemodynamic responses. The effects of volatile anaesthetics on adrenomedullin-induced haemodynamic responses, however, are unclear. We hypothesized that the volatile anaesthetic isoflurane inhibits adrenomedullin-induced haemodynamic responses. We studied the effects of isoflurane on adrenomedullin-induced haemodynamic responses in pithed rats, which enables us to evaluate the direct cardiovascular effects of drugs without interference from centrally mediated circulatory reflexes.

Male Wistar rats were pithed by inserting a stainless-steel rod into the spinal cord. Following median sternotomy, a flow probe was placed around the ascending aorta to measure aortic blood flow. Mean arterial pressure and cardiac output were maintained at approximately 100 mmHg and 50 mL min−1, respectively, with continuous infusion of norepinephrine. After 30 min inhalation of isoflurane (1%, or 2%) in oxygen, or only oxygen, adrenomedullin (1, 3, 10 or 30 μg kg−1) was administered intravenously.

Adrenomedullin administration induced a transient increase followed by a persistent decrease in mean arterial pressure and cardiac output. Isoflurane (2%) significantly inhibited the initial increase in mean arterial pressure and the later decrease in mean arterial pressure and systemic vascular resistance.

Isoflurane inhibits adrenomedullin-induced vasodilation and positive inotropic effect in pithed rats. Isoflurane might inhibit the adrenomedullin receptor-mediated response, which is a common pathway for both actions.

Limited and inconsistent data exist on simple, readily available predictors of long-term mortality of critically ill chronic obstructive pulmonary disease patients requiring invasive mechanical ventilation. We therefore examined the influence of arterial blood gas derangement and burden of comorbidities on 90-day and 1-yr mortality of chronic obstructive pulmonary disease patients treated with invasive mechanical ventilation.

We identified all chronic obstructive pulmonary disease patients (n = 230) treated with invasive mechanical ventilation between 1994 and 2004 at a Danish primary-level hospital. Data on arterial blood gas specimens and comorbidity were obtained from medical records and Hospital Discharge Registries. We used Cox’s regression analysis to estimate mortality ratios according to arterial blood gas values and level of comorbidity.

Ninety-day and 1-yr mortality among chronic obstructive pulmonary disease patients requiring invasive mechanical ventilation was 30.8% and 40.5%, respectively. All 90-day and 1-yr mortality ratios according to arterial blood gas values were close to one and one was included in all 95% CI. Among patients with a high level of comorbidity 90-day mortality ratio was 1.3 (95% CI: 0.6–2.7) when compared with patients without comorbidity. The corresponding 1-yr mortality ratio was 1.4 (95% CI: 0.7–2.9).

Chronic obstructive pulmonary disease patients treated with invasive mechanical ventilation have substantial long-term mortality. Neither the levels of arterial blood gas values measured immediately before invasive mechanical ventilation was initiated nor the burden of comorbidity were strong determinants of long-term mortality among these patients.

The aetiology of parenteral nutrition-associated hepatic injury remains unresolved. The aim of the study was to evaluate the effects of structured triglycerides in parenteral nutrition compared either to a physical medium-chain triglycerides (MCT)/long-chain triglcerides (LCT) mixture or to a LCT emulsion on hepatic integrity.

In a randomized, double-blinded trial, we studied 45 patients undergoing abdominal surgery, who were expected to receive parenteral nutrition for 5 days. Patients were allocated to one of three nutrition regimens: Group A (n = 15) received structured triglycerides, Group B (n = 15) a MCT/LCT and Group C (n = 15) a LCT lipid emulsion. Before the start of parenteral nutrition (T0), 24 h (T1), 48 h (T2), 72 h (T3) and 120 h (T4) after start of infusion the following parameters were measured: Alpha-glutathione S-transferase (α-GST), alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose and serum triglycerides.

At T3 and T4, α-GST levels were significantly higher in Group B (T3: 9.4 ± 9.9; T4: 14.6 ± 19.5 μg L−1) and Group C (T3: 14.2 ± 20.8; T4: 22.4 ± 39.3 μg L−1) compared with the patients receiving structured triglycerides (T3: 1.9 ± 1.8; T4: 3.2 ± 2.7 μg L−1). Whereas the mean α-GST-levels in structured triglycerides group always remained in the normal range, this was not the case in both other groups at T3 and T4. There were no significant differences concerning ALT, AST and glucose levels. At T3 and T4, triglyceride levels were significantly lower in Group A than in Groups B and C.

Hepatic integrity was well retained with the administration of structured triglycerides, whereas both MCT/LCT emulsion and LCT emulsion caused subclinical hepatic injury.

Stewart’s and Fencl’s methods have recently been proposed to interpret acid–base disorders where traditional theory has proven inadequate. Our objectives were to evaluate: (1) the occurrence of acid–base disturbances in critically ill patients and their trend over the first 3 intensive care unit days, (2) whether Stewart’s theory offers advantages over the traditional theory in the diagnosis of acid–base metabolic disturbances and (3) whether variables derived from Stewart’s and Fencl’s methods offer advantages over the traditional method to predict patient mortality.

A prospective cohort study in a general intensive care unit. Blood samples were analysed for arterial blood gases, electrolytes and proteins. PaCO2, pH, bicarbonate, base excess, standard base-excess, sodium, potassium, chloride, phosphorous, calcium, magnesium and lactate were measured. Anion gap, Stewart’s and Fencl’s variables were calculated.

When using Stewart’s method, metabolic acidosis and metabolic alkalosis were found in 92.9% and 93.4% of samples, respectively. Corresponding figures obtained with the traditional method were 15% and 18.7%. In 245 (64.5%) samples, Stewart’s method revealed that metabolic acidosis and alkalosis were simultaneously present, whereas the traditional method revealed a normal acid–base status. Strong ion gap increased significantly over the first 3 intensive care unit days. Strong ion gap and lactate were independent predictors of 28-day mortality.

Metabolic acidosis by unmeasured anions is a clinically relevant phenomenon, which is correlated with mortality. Progressive metabolic acidosis may be ongoing in the early phase of critical illness despite the absence of acidaemia.

For neuromuscular blocking agents, an inverse relationship between potency and time to peak effect has been observed. To test the hypothesis that this relationship is due to buffered diffusion, we investigated the influence of dose on time to peak effect. Pharmacokinetic–pharmacodynamic simulations were performed to support the expected relationships between potency, dose, peak effect and time to peak effect.

Pigs (20–28 kg body weight) were anaesthetized with ketamine and midazolam, followed by pentobarbital and fentanyl intravenously. Neuromuscular block was measured by stimulating the peroneal nerve supramaximally at 0.1 Hz and measuring the response of the tibialis anterior muscle mechanomyographically. After an initial dose to establish the individual ED90 of a neuromuscular blocking agent (rocuronium, vecuronium, pipecuronium or d-tubocurarine), five different doses of the same compound were administered to each animal, aiming at 20%, 40%, 60%, 75% or 90% block, in a random order. Doses were given 45 min after complete recovery of the twitch response.

For rocuronium and pipecuronium, time to peak effect increased with dose, whereas dose did not affect time to peak effect of vecuronium and d-tubocurarine. Simulations predict that time to peak effect decreases with dose if buffered diffusion is taken into account.

The results suggest that buffered diffusion does not play a dominant role in the time to peak effect of neuromuscular blocking agents. Therefore it is unlikely that the observed inverse relationship between potency and time to peak effect of neuromuscular blocking agents in the clinical range is due to buffered diffusion.

This study investigated the neuroprotective effect of acute normovolaemic haemodilution with a novel hydroxyethyl starch (130/0.4, HES) on focal cerebral ischaemia-reperfusion injury and determined optimum degree for haemodilution in the rat.

Male Sprague-Dawley rats were randomly divided into three groups (n = 10 each): hydroxyethyl starch, saline and controls. Animals in the hydroxyethyl starch and saline groups were haemodiluted until haematocrit decreased to 30% of baseline. In another experiment male Sprague-Dawley rats were randomly assigned to four groups (n = 10 each): HES30, HES25 and HES20 and controls. Rats in the HES30, HES25 and HES20 groups were haemodiluted with hydroxyethyl starch until the haematocrit decreased to 30%, 25% and 20%, respectively. At 15 min after haemodilution, all the rats were subjected to a right middle cerebral artery occlusion for 120 min. Neurologic deficit scores and infarct volumes were assessed 24 h after reperfusion.

Haemodilution with hydroxyethyl starch improved neurologic outcome (P < 0.01) and reduced infarct volume (P < 0.01) compared to saline and controls. Haemodilution with saline augmented infarct volume (P < 0.05 vs. controls). Neurologic deficit scores in HES30 and HES25 groups were significantly lower compared to controls (P < 0.05) while infarct volumes in controls and HES20 were significantly larger compared to HES30 and HES25 (P < 0.01).

This study demonstrates that acute normovolaemic haemodilution with a novel hydroxyethyl starch (130/0.4) reduces infarct volume and improves neurological outcome after focal cerebral ischaemia in a rat stroke model. Neuroprotection by haemodilution was highest at haematocrit dilution between 25% and 30%, while ischaemic injury was exacerbates when haematocrit was diluted to 20%.

There is increasing evidence of gender differences in the pharmacokinetics and pharmacodynamics of aminosteroid neuromuscular blocking agents. Compared to males, females are more susceptible, requiring approximately 30% less rocuronium to achieve the same degree of neuromuscular block. However, little information is available whether this difference is applicable to modern benzylisoquinolines (cisatracurium).

In all, 848 patients (423 males, 425 females) undergoing general surgery under total intravenous anaesthesia with muscle relaxation, tracheal intubation and mechanical ventilation were studied. Patients were randomized to receive a single bolus dose of cisatracurium (0.1 mg kg−1, 221 males and 199 females) or rocuronium (0.6 mg kg−1, 202 males and 226 females). The onset time for 95% depression of T1, clinical duration until 25% recovery and recovery index (T1 from 25% to 75%) were determined with an NMT electromyographic module of the Datex-Ohmeda S/5 Anaesthesia Monitor. The data for male and female groups were compared with appropriate statistical tests (unpaired t-test, Mann–Whitney rank sum test and Fisher’s exact test).

In both groups (cisatracurium and rocuronium), males were significantly taller (P < 0.001) and heavier (P < 0.001) than females, but the body mass index was comparable. For rocuronium, the onset time was shorter 91.7 ± 14.3 s vs. 108.0 ± 14.6 s (P < 0.001) and the clinical duration was increased in females 43.3 ± 7.8 min vs. 31.3 ± 5.5 min (P < 0.001). In the cisatracurium group, both onset times (248.9 ± 60.7 s for males vs. 253.4 ± 70.9 s for females) and clinical duration (42.6 ± 6.9 min for males vs. 43.1 ± 6.9 min for females) were similar. The recovery index was identical for males and females in both groups.

Females were more sensitive than males to a single bolus dose of rocuronium. Under the study conditions described, the onset time was shorter and the clinical duration was increased in female patients. This suggests that the routine dose of rocuronium should be reduced in females compared to males. On the contrary, we could demonstrate no gender differences in the onset time or clinical duration of cisatracurium.