Hypotension due to spinal anesthesia influences fetal circulation in primary caesarean sections.

PURPOSE: Hypotension due to spinal anesthesia is a well-known side effect in pregnant women receiving caesarean section. Little is known about its impact on fetal blood circulation. METHODS: 40 women with uncomplicated singleton term pregnancies prepared for caesarean section were prospectively evaluated by Doppler sonography before and immediately after spinal anesthesia. RESULTS: In 90% of the women, blood pressure significantly decreased after spinal anesthesia and 42.5% of the patients suffered from severe hypotension. We found a significant negative correlation between maternal blood pressure change and the resistant index (RI) of the umbilical artery (rs = - 0.376, p = 0.017) and a significant positive correlation between maternal blood pressure and fetal middle cerebral artery. CONCLUSION: Healthy fetuses seem to compensate well in situations with decreased uteroplacental blood flow due to maternal hypotension measured by means of RI changes in the fetal umbilical and middle cerebral artery. This raises the question if growth-restricted and/or preterm fetuses are able to compensate similarly or if general anesthesia would be a method of choice.

N-terminal prohormone of brain natriuretic peptide: a useful tool for the detection of acute pulmonary artery embolism in post-surgical patients.

BACKGROUND: Acute pulmonary embolism (APE) is an important clinical problem in patients after major surgery and often remains a difficult diagnosis because of unspecific clinical symptoms. Therefore, we investigated the role of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) for the detection of APE. METHODS: In 44 patients with suspected APE referred to the intensive care unit after major surgery, serum NT-proBNP, troponin-I, and D-dimers were measured according to the standard hospital protocol. To definitively confirm or exclude APE, all patients underwent an angiographic CT scan of the thorax. RESULTS: APE was confirmed in 28 and excluded in 16 patients by CT scan. NT-proBNP was significantly (P<0.01) higher in patients with APE [4425 (sd 8826; range 63-35 000) pg ml(-1)] compared with those without [283 (sd 327; range 13-1133) pg ml(-1)]. The sensitivity of the NT-proBNP screening was 93%, specificity 63%, positive predictive value 81%, and negative predictive value 83%. There were no significant (P = 0.96) differences in D-dimers between subjects with and without APE [confirmed APE: 511 (sd 207; range 83-750) µg litre(-1); excluded APE: 509 (sd 170; range 230-750) µg litre(-1)]. Troponin-I levels were not elevated in 32% of the patients with APE. CONCLUSIONS: D-dimer levels are frequently elevated in post-surgical patients and not applicable for confirmation or exclusion of APE. In contrast, NT-proBNP appears to be a useful biomarker for APE diagnosis in the postoperative setting. In the case of NT-proBNP levels below the upper reference limit, haemodynamically relevant APE is unlikely. Troponin-I in contrast is not considered to be helpful.

Intranasal application of xenon: describing the pharmacokinetics in experimental animals and the increased pain tolerance within a placebo-controlled experimental human study.

BACKGROUND: Pain sensitizes the central nervous system via N-methyl-D-aspartate receptors (NMDARs) leading to an enhancement of pain perception. However, the enhanced responsiveness of pain-processing areas can be suppressed by subanaesthetic doses of the NMDAR antagonist xenon. To analyse the strength of the analgesic effect of low-dose xenon using new economical application methods, we tested xenon applied nasally in an experimental human pain setting. METHODS: We tested 10 healthy volunteers using a multimodal experimental pain testing in a randomized double-blind placebo-controlled repeated measures study. Xenon was administered using a novel low-pressure intranasal application device. Additionally, we measured xenon concentrations in blood samples obtained from intracranial veins of experimental animals to describe the pharmacokinetics of intranasally applied xenon in the cerebral compartment. RESULTS: Intranasal application of xenon at a rate of 1.0 litre h(-1) for 30 min significantly increased pain tolerance of volunteers to ischaemic (+128%), cold (+58%), and mechanical (+40%) stimulation (P<0.01). However, 60 min after terminating the application of xenon, there was no significant alteration of pain tolerance compared with placebo. Cranial blood concentrations of xenon in pigs reached a steady state of approximately 450 nl ml(-1) after 5 min. CONCLUSIONS: In this placebo-controlled experimental human study, we described the increased pain tolerance induced by intranasally applied xenon. On the basis of our results, we conclude that intranasally administered xenon has analgesic properties and suggest that the novel application device presented here offers new possibilities for the administration of NMDAR antagonists within a multimodal analgesia approach.

Arterial and mixed venous xenon blood concentrations in pigs during wash-in of inhalational anaesthesia.

There are no data available on the kinetics of blood concentrations of xenon during the wash-in phase of an inhalation anaesthesia aiming at 1 MAC end-expiratory concentration. Therefore, we anaesthetized eight pigs with continuous propofol and fentanyl and measured arterial, mixed venous and end-expiratory xenon concentrations by gas chromatography-mass spectrometry 1, 2, 3, 4, 5, 7, 10, 15, 20, 30, 60 and 120 min after starting the anaesthetic gas mixture [67% xenon/33% oxygen; 3 litre x min(-1) during the first 10 min, thereafter minimal flow with 0.48 (SD 0.03) litre x min(-1)]. End-expiratory xenon concentrations plateaued (defined as <5% change from the preceding value) at 64 (6) vol% after 7 min, and arterial and mixed venous xenon concentrations after 5 and 15 min respectively. The highest arterio-venous concentration difference occurred after 3 min. Using the Fick principle, we calculated a mean xenon uptake of 3708 (829) and 9977 (3607) ml after 30 and 120 min respectively.

Effects on haemodynamics and catecholamine release of xenon anaesthesia compared with total i.v. anaesthesia in the pig.

In order to investigate haemodynamic response and catecholamine release during anaesthesia with xenon, we conducted a study on 28 pigs which were allocated randomly to one of four groups: total i.v. anaesthesia with pentobarbitone and buprenorphine, and xenon anaesthesia with inspiratory concentrations of 30%, 50% or 70%, respectively, supplemented with pentobarbitone. Haemodynamic variables were measured using arterial and Swan Ganz catheters. Depth of anaesthesia was monitored using spectral edge frequency analysis. Plasma concentrations of dopamine, noradrenaline and adrenaline were measured by high pressure liquid chromatography. All haemodynamic variables and plasma concentrations of dopamine and noradrenaline remained within normal limits. Adrenaline concentrations were reduced significantly in all groups. Xenon anaesthesia was associated with a high degree of cardiovascular stability. Significant reduction in adrenaline concentrations at inspiratory xenon concentrations of 30% and 50% can be explained by analgesic effects of xenon below its MAC value.

Xenon does not induce contracture in human malignant hyperthermia muscle.

Xenon has many characteristics of an ideal anaesthetic agent. It is not known whether xenon is a safe alternative to the potent inhalational anaesthetics in patients susceptible to malignant hyperthermia (MH). We investigated the effect of xenon, halothane and caffeine on muscle specimens of 31 individuals, referred to the MH Unit of the University of Ulm, and performed genetic epidemiology. Thirteen individuals were classified as MH susceptible and 18 as MH negative. Xenon 70% did not cause an increase in baseline tension of any MH-susceptible muscle specimen in contrast to halothane and caffeine. The evoked twitch response increased transiently in MH-susceptible and normal specimens indicating a mechanism independent of MH susceptibility. These results suggest that xenon, in concentrations up to 70% may be a safe anaesthetic for MH-susceptible patients.

Xenon does not trigger malignant hyperthermia in susceptible swine.

BACKGROUND: Xenon is a noble gas with anesthetic properties currently under investigation for use in humans. This study was performed to evaluate whether xenon may trigger malignant hyperthermia in susceptible swine. METHODS: Nine malignant hyperthermia-sensitive swine (Pietrain) were initially anesthetized with pentobarbital and then ventilated with 70% xenon in oxygen for 2 h. Heart rate, mean arterial pressure, cardiac output, body temperature, arterial and mixed-venous blood gases, and plasma catecholamine and lactate levels were measured every 10 min both during xenon-oxygen ventilation and after a 30-min xenon washout phase followed by subsequent administration of halothane (1% inspired) and succinylcholine (3 mg/kg intravenous). During the investigation, no malignant hyperthermia-specific therapy was instituted. RESULTS: Xenon exposure did not induce any changes in metabolic and hemodynamic parameters nor elevations of the plasma catecholamine levels indicative for an episode of malignant hyperthermia. By contrast, in all animals, within 20 min after the administration of halothane and succinylcholine, fulminant and fatal malignant hyperthermia episodes were initiated. CONCLUSIONS: The authors conclude that xenon does not trigger malignant hyperthermia in susceptible swine.