Non-invasive assessment of fluid responsiveness using CNAP™ technology is interchangeable with invasive arterial measurements during major open abdominal surgery.

BACKGROUND: Dynamic variables of fluid responsiveness (FR), such as pulse pressure variation (PPV), have been shown to predict the response to a fluid challenge accurately. A recently introduced non-invasive technology based on the volume-clamp method (CNAP™) offers the ability to measure PPV continuously (PPVCNAP). However, the accuracy regarding the prediction of FR in the operating room has to be proved. METHODS: We compared PPVCNAP with an invasive approach measuring PPV using the PiCCO technology (PPVPiCCO). We studied 47 patients undergoing major open abdominal surgery before and after a passive leg-raising manoeuvre and i.v. fluid resuscitation. A positive response to a volume challenge was defined as ≥15% increase in stroke volume index obtained with transpulmonary thermodilution. Bootstrap methodology was used with the grey zone approach to determine the area of inconsistency regarding the ability of PPVPiCCO and PPVCNAP to predict FR. RESULTS: In response to the passive leg-raising manoeuvre, PPVPiCCO predicted FR with a sensitivity of 81% and a specificity of 72% [area under the curve (AUC) 0.86] compared with a sensitivity of 76% and a specificity of 72% (AUC 0.78) for PPVCNAP Regarding the volume challenge in the operating room, PPVPiCCO predicted FR with a sensitivity of 87% and a specificity of 100% (AUC 0.97) compared with a sensitivity of 91% and specificity of 93% (AUC 0.97) for PPVCNAP The grey zone approach identified a range of PPVPiCCO values (11-13%) and PPVCNAP values (7-11%) for which FR could not be predicted reliably. CONCLUSIONS: Non-invasive assessment of FR using PPVCNAP seems to be interchangeable with PPVPiCCO in patients undergoing major open abdominal surgery. CLINICAL TRIAL REGISTRATION: NCT02166580.

Sufentanil administration guided by surgical pleth index vs standard practice during sevoflurane anaesthesia: a randomized controlled pilot study.

BACKGROUND: Evaluation of analgesia and antinociception during anaesthesia is still a challenging issue and routinely based on indirect and non-specific signs such as movement, tachycardia, or lacrimation. Recently, the surgical pleth index (SPI) derived by finger plethysmography was introduced to detect nociceptive stimulation during anaesthesia. While SPI guidance reduced the number of unwanted events during total i.v. anaesthesia (TIVA), the impact of SPI during volatile-based anaesthesia with intermittent opioid administration has not yet been elucidated. METHODS: Ninety-four patients were randomized into either SPI-guided analgesia or standard practice (Control). In both groups, anaesthesia was maintained with sevoflurane to keep bispectral index values between 40 and 60. In the SPI group, patients received a sufentanil bolus (10 µg) whenever SPI value increased above 50, whereas in the control group, sufentanil was administered according to standard clinical practice. The number of unwanted somatic events, haemodynamics, sufentanil consumption, and recovery times were recorded. RESULTS: The incidence of intraoperative unwanted somatic events was comparable between the groups (P=0.89). No significant differences with respect to hypotensive or hypertensive events were found. The mean (95% confidence interval) sufentanil consumption was non-significantly (P=0.07) reduced in the SPI group, 0.64 (0.57-0.71) vs 0.78 (0.64-0.91) µg min(-1). Recovery times were comparable between the groups. CONCLUSIONS: Sufentanil administration guided by SPI during sevoflurane anaesthesia is clinically feasible. In contrast to TIVA, it did not improve anaesthesia conduct with respect to unwanted somatic events, haemodynamic stability, sufentanil consumption, emergence time, or post-anaesthesia care unit care. Therefore, we conclude that anaesthesia regimen has an impact on beneficial effects by SPI guidance. Clinical trial registration NCT01525537. (Registered at Clinicaltrials.gov.).

Effect of propofol on hypoxia re-oxygenation induced neuronal cell damage in vitro*.

Propofol may protect neuronal cells from hypoxia re-oxygenation injury, possibly via an antioxidant actions under hypoxic conditions. This study investigated the molecular effects of propofol on hypoxia-induced cell damage using a neuronal cell line. Cultured human IMR-32 cells were exposed to propofol (30 µm) and biochemical and molecular approaches were used to assess cellular effects. Propofol significantly reduced hypoxia-mediated increases in lactate dehydrogenase, a marker of cell damage (mean (SD) for normoxia: 0.39 (0.07) a.u.; hypoxia: 0.78 (0.21) a.u.; hypoxia+propofol: 0.44 (0.17) a.u.; normoxia vs hypoxia, p<0.05; hypoxia vs hypoxia+propofol, p<0.05), reactive oxygen species and hydrogen peroxide. Propofol also diminished the morphological signs of cell damage. Increased amounts of catalase, which degrades hydrogen peroxide, were detected under hypoxic conditions. Propofol decreased the amount of catalase produced, but increased its enzymatic activity. Propofol protects neuronal cells from hypoxia re-oxygenation injury, possibly via a combined direct antioxidant effect along with induced cellular antioxidant mechanisms.

Detection of hypotension during Caesarean section with continuous non-invasive arterial pressure device or intermittent oscillometric arterial pressure measurement.

BACKGROUND: The intensified use of spinal anaesthesia (SPA) for Caesarean section significantly contributed to a decreased maternal mortality and morbidity. Nevertheless, one of the major side-effects is hypotension after SPA with potential negative effects on the fetus. Owing to discontinuous oscillometric measurements (non-invasive arterial pressure, NIAP), hypotensive episodes may be missed. Recently, a continuous NIAP measurement device (CNAP) with acceptable agreement with the mean invasive AP was introduced. We hypothesized that CNAP detects hypotensive episodes more reliably compared with NIAP measurements. METHODS: A total of 65 women undergoing Caesarean section under SPA were included in the study analysis. A total of 888 NIAP measurements obtained at 3 min cycles, starting from before SPA and continued until delivery, were analysed. RESULTS: When averaged over all cycles, the lowest systolic AP identified by CNAP in each cycle [105 mm Hg, (24.4)] was significantly lower (P<0.001) than the average of the individual corresponding single NIAP measurements [126 mm Hg (22.1)] and highest CNAP average [126 mm Hg (24.5)]. Hypotension (systolic AP <100 mm Hg) was detected in 39% of all cycles with CNAP and in 9% with NIAP. Hypotension was detected in 91% of the patients based on CNAP and in 55% based on NIAP. Fetal acidosis defined by an umbilical vein pH under 7.25 did not occur when the lowest systolic AP measured by CNAP was above 100 mm Hg. CONCLUSIONS: The CNAP device detected more hypotensive episodes after SPA and significantly lower AP compared with NIAP. AP monitoring based on CNAP may improve haemodynamic management in this patient population with potential benefit for the fetus.

The effect of posture and anaesthetic technique on the surgical pleth index.

The surgical pleth index has been shown to correlate with surrogate variables of nociception during general anaesthesia, and it has been suggested to be of use as a depth of anaesthesia monitor. However, little is known about confounding factors. As the main determining variables are based on both central and peripheral autonomic regulatory mechanisms, we hypothesised that changing a patient`s posture may produce a marked effect. We studied the effects of posture change in 45 patients who were randomly assigned to receive general (n = 15) or spinal anaesthesia with (n = 15) or without sedation (n = 15), as well as 15 awake volunteers. Mean (SD) values of the surgical pleth index after adoption of the lithotomy position were reduced from 57 (22) to 21 (6) under general anaesthesia, 63 (15) to 31 (9) under spinal anaesthesia alone, and 52 (14) to 22 (8) under spinal anaesthesia with sedation (all p < 0.01). In healthy volunteers, the surgical pleth index increased from 37 (13) to 57 (11) (p < 0.01) after 30° head-up tilt and was reduced from 35 (11) to 25 (11) after head-down tilt (p < 0.05). Change in posture has a marked effect on the surgical pleth index which lasts for at least 45 min, and this must be considered when interpreting the displayed values.

The effect of short time periods of pre-operative warming in the prevention of peri-operative hypothermia.

The aim of our study was to evaluate the performance of different durations of active pre-operative skin-surface warming (pre-warming) to prevent peri-operative hypothermia and postoperative shivering. We randomly assigned 200 patients, scheduled for surgery of 30-90 min under general anaesthesia, to receive passive insulation or forced-air skin surface warming for 10, 20 or 30 min. Body temperature was measured at the tympanic membrane. Shivering was graded by visual inspection. There were significant differences in changes of core temperature between the non-pre-warmed group and all the pre-warmed groups (p < 0.00001), but none between the three pre-warmed groups (p = 0.54). Without pre-warming, 38/55 (69%) patients became hypothermic (< 36 °C) at the end of anaesthesia, whereas only 7/52 (13%), 3/43 (7%) and 3/50 (6%) patients following 10, 20 or 30 min pre-warming, respectively, became hypothermic (p < 0.001 vs no pre-warming). Shivering was observed in 10 patients without, and in three, three and one patients with pre-warming in the respective groups (p = 0.02). Pre-warming of patients for only 10 or 20 min before general anaesthesia mostly prevents hypothermia and reduces shivering.

A comparison of the Nexfin® and transcardiopulmonary thermodilution to estimate cardiac output during coronary artery surgery.

The newly introduced Nexfin(®) device allows analysis of the blood pressure trace produced by a non-invasive finger cuff. We compared the cardiac output derived from the Nexfin and PiCCO, using transcardiopulmonary thermodilution, during cardiac surgery. Forty patients with preserved left ventricular function undergoing elective coronary artery bypass graft surgery were studied after induction of general anaesthesia and until discharge to the intensive care unit. There was a significant correlation between Nexfin and PiCCO before (r(2) = 0.81, p < 0.001) and after (r(2) = 0.56, p < 0.001) cardiopulmonary bypass. Bland-Altman analysis demonstrated the mean bias of Nexfin to be -0.1 (95% limits of agreement -0.6 to +0.5, percentage error 23%) and -0.1 (-0.8 to +0.6, 26%) l.min(-1).m(-2), before and after cardiopulmonary bypass, respectively. After a passive leg-raise was performed, there was also good correlation between the two methods, both before (r(2) = 0.72, p < 0.001) and after (r(2) = 0.76, p < 0.001) cardiopulmonary bypass. We conclude that the Nexfin is a reliable method of measuring cardiac output during and after cardiac surgery.

Accuracy of the pleth variability index to predict fluid responsiveness depends on the perfusion index.

BACKGROUND: Respiratory variations in plethysmographic waveform amplitudes derived from pulse oximetry are believed to predict fluid responsiveness. The non-invasive pleth variability index (PVI) is a variable based on the calculation of changes in the perfusion index (PI). The aim of the following study was to examine whether the predictive power of PVI depends on different values of PI. METHODS: Eighty-one patients undergoing elective coronary artery surgery were studied before operation: at baseline after induction of anaesthesia and during passive leg raising (PLR). Each patient was monitored with central venous pressure (CVP), the PiCCO monitor and the non-invasive Masimo monitoring system. Stroke volume index by transpulmonary thermodilution (SVI(TPTD)), pulse pressure variation (PPV), stroke volume variation (SVV) and systemic vascular resistance index (SVRI) were measured using the PiCCO monitoring system. PI and PVI were obtained by pulse oximetry. RESULTS: Responders were defined to increase their SVI(TPTD) >15% after PLR. The highest area under the curve (AUC) was found for PPV (AUC: 0.83, P<0.0001) and SVV (AUC: 0.72, P=0.002), in contrast to PVI (AUC: 0.60, P=0.11) and CVP (AUC: 0.60, P=0.13). The accuracy of PVI to predict fluid responsiveness was improved on analysing patients with higher PI values. PI of about 4% (n=45) achieved statistical significance (AUC: 0.72, P=0.01). CONCLUSION: The PVI was not able to predict fluid responsiveness with sufficient accuracy. In patients with higher perfusion states, the PVI improved its ability to predict haemodynamic changes, strongly suggesting a relevant influence of the PI on the PVI.

Clinically relevant asymmetry of bispectral index during recovery from anaesthesia for ear-nose-throat surgery in adults and children.

This study investigates the incidence of clinically relevant asymmetry in bispectral index readings from different sides of the skull (using two monitors) during ear-nose-throat surgery in 42 adults and 46 children. A unilateral increase or decrease > 10% from baseline was defined as an 'asymmetry'. Asymmetry followed by movement after stimulation was defined as a 'clinically relevant asymmetry'. Asymmetry occurred in 39 out of 42 adults (93%) and in 20 out of 46 children (44%) during surgery and in 24 out of 42 adults (57%) and in 17 out of 46 children (37%) during recovery. Clinically relevant asymmetry was observed in 5 out of 42 adults (12%) and 6 out of 46 children (13%). The incidence of asymmetry was higher in adults during surgery (p = 0.0002). In conclusion, clinically relevant bispectral index asymmetry has been observed in > 10% of paediatric and adult anaesthesia and may have clinical implications. You can respond to this article at http://www.anaesthesiacorrespondence.com.

Non-invasive prediction of fluid responsiveness in infants using pleth variability index.

This prospective study assessed whether respiratory variations in velocity time integral, peak blood flow velocity and non-invasive pleth variability index are useful measurements in infants undergoing congenital heart surgery and determined threshold values that may help guide fluid administration. In 27 infants receiving mechanical ventilation, of mean (SD) weight 10.4 (6.3) kg, 13 increased their stroke volume index ≥ 15% following a fluid challenge and 14 did not. The best area under the receiver operating characteristic curve was for the echocardiographic-derived variables respiratory variation in blood peak flow velocity (area under the ROC curve = 0.92; p = 0.0002) and respiratory variation of the velocity time integral (area under the ROC curve = 0.84; p = 0.002). The pleth variability index also predicted fluid responsiveness (area under the ROC curve = 0.79; p = 0.01), in contrast to heart rate (area under the ROC curve = 0.53; p = 0.75) and central venous pressure (area under the ROC curve = 0.57; p = 0.52).

Surgical stress index in response to pacemaker stimulation or atropine.

BACKGROUND: The surgical stress index (SSI) is a new monitoring tool for the assessment of nociception during general anaesthesia. It is calculated based on the heart beat interval and the pulse wave amplitude. Correlation of SSI with nociceptive stimuli and opioid effect-site concentrations has been demonstrated, but the influence of isolated modulation of heart rate (HR) on SSI is still unclear. The aim of this study was to evaluate the effect on SSI of atropine administration and cardiac pacing. METHODS: In 18 anaesthetized ASA III ICU patients, either repetitive cardiac pacemaker stimulation or administration of atropine (10 microg kg(-1)) was performed, and the effect on SSI, arterial pressure, spectral entropy, and bispectral index was analysed. RESULTS: Cardiac pacing at 100 beats min(-1) was followed by an increase in SSI from 26 [17-35 (10-41)] to 59 [53-72 (48-78)] {median [inter-quartile range (range)]} (P=0.0006), whereas other variables remained unaffected. Also, atropine administration increased SSI from 27 [20-34 (16-39)] to 58 [48-70 (41-81)] (P=0.007) without significant effect on other variables except HR. A recalibration of SSI during cardiac pacing leads to a significant decrease in SSI to 49 [40-52 (36-57)] (P=0.03), whereas recalibration after atropine administration had no effect. CONCLUSIONS: SSI values measured in patients receiving atropine or in patients with pacemakers should be interpreted cautiously.

Evaluation of the surgical stress index during spinal and general anaesthesia.

BACKGROUND: Although in modern anaesthesia, monitoring depth of anaesthesia and quality of neuromuscular block are routine, monitoring of analgesia still remains challenging. Recently, the surgical stress index (SSI), derived from finger photoplethysmographic signal, was introduced as a surrogate variable reflecting the nociception-antinociception balance. This study aimed at evaluating the SSI in patients undergoing regional anaesthesia either alone or combined with sedation compared with patients undergoing general anaesthesia (GA). METHODS: Seventy-one patients undergoing general (n=24) or spinal anaesthesia with (n=24) or without sedation (n=23) were included. SSI was measured the day before surgery and at defined time points during anaesthesia and surgery and also in the recovery room. SSI was compared with haemodynamic variables like heart rate and systolic arterial pressure. RESULTS: The SSI was higher in patients undergoing spinal anaesthesia [mean 65, CI (59.3-70.5)] compared with GA [48 (39.9-56.4), P<0.01], and baseline [41 (37.3-44.2), P<0.001]. During spinal anaesthesia with sedation [44 (36.2-50.9)], it was comparable with the baseline level (P>0.05). In comparison with baseline, SSI in the recovery room was higher in patients after GA [59 (48.4-67.9), P<0.025] but not after spinal anaesthesia [53 (47.6-60.1), P>0.05] or after spinal anaesthesia with sedation [54 (45.8-65.1), P>0.05]. Changes of the SSI were not reflected by changes of haemodynamic variables. CONCLUSIONS: In fully awake patients under spinal anaesthesia, the SSI does not reflect the nociception-antinociception balance. This may be due to the influence of mental stress on the sympathetic nervous system. Even light sedation attenuates these influences.

Differences between bispectral index and spectral entropy during xenon anaesthesia: a comparison with propofol anaesthesia.

We enrolled 114 patients, aged 65-83 years, undergoing elective surgery (duration > 2h) into a randomised, controlled study to evaluate the performance of bispectral index and spectral entropy for monitoring depth of xenon versus propofol anaesthesia. In the propofol group, bispectral index and state entropy values were comparable. In the xenon group, bispectral index values resembled those in the propofol group, but spectral entropy levels were significantly lower. Mean arterial blood pressure was higher and heart rate was lower in the xenon group than in the propofol group. Bispectral index and spectral entropy considerably diverged during xenon but not during propofol anaesthesia. We therefore conclude that these measures are not interchangeable for the assessment of depth of hypnosis and that bispectral index is likely to reflect actual depth of anaesthesia more precisely compared with spectral entropy.

Influence of anaesthesia resident training on the duration of three common surgical operations.

We investigated the influence of resident training on anaesthesia workflow of three standard procedures--laparoscopic cholecystectomy, diagnostic gynaecological laparoscopy and transurethral prostate gland resection (TURP)--comparing 259 non-emergency resident vs 341 consultant cases from 20 German hospitals. Each hospital provided 10 random cases for each procedure, yielding 600 cases for analysis. Standard time intervals as documented in the hospital information system were: 'Case Time' (the time from the start of anaesthesia induction to discharge of the patient to the recovery area) and 'Anaesthesia Control Time' (which was the Case Time minus the time from the start of surgery to the end of surgical closure). Case Time was significantly shorter for consultants in all three procedures (p < 0.05, analysis of variance) and Anaesthesia Control Time shorter for consultants only in gynaecological laparoscopy and TURP. Patient comorbidity, patient age and geographical location of the hospital were not influential factors in the analysis of variance. We conclude that resident training significantly increases duration of elective operative times.

Pulse pressure variation and stroke volume variation during different loading conditions in a paediatric animal model.

BACKGROUND: Previous studies in adult patients and animal models have demonstrated that pulse pressure variation (PPV) and stroke volume variation (SVV) can be used to predict the response to fluid administration. Currently, little information is available on the performance of these variables in infants and neonates. The aim of our study was to assess whether PPV and SVV can predict fluid responsiveness in an animal model and to investigate the influence of different tidal volumes applied. METHODS: PPV and SVV were monitored by pulse contour analysis in 19 anaesthetized and paralysed piglets during ventilation with tidal volumes (V(T)) of 5, 10 and 15 ml/kg both before and after fluid loading with 25 ml/kg of hydroxy-ethyl starch 6% (HES). Cardiac output was measured by pulmonary artery thermodilution and a positive response to HES infusion was defined as >/=20% increase in the stroke volume index (SVI). RESULTS: Before HES infusion, PPV and SVV were significantly greater during ventilation with a V(T) of 10 and 15 ml/kg than during ventilation with a V(T) of 5 ml/kg (P<0.05). After HES infusion, only ventilation with V(T) 15 ml/kg resulted in a significant increase in PPV and SVV. As assessed by receiver operating characteristic curve analysis, SVV during ventilation with V(T) 10 ml/kg was the best predictor of a positive response to fluid loading (AUC=0.87). CONCLUSIONS: In this paediatric animal model, we found that SVV during ventilation with 10 ml/kg was a sensitive and specific predictor of the response to fluid loading.

Does heart rate variability predict hypotension and bradycardia after induction of general anaesthesia in high risk cardiovascular patients?

This study investigated whether heart rate variability predicts haemodynamic events in high risk patients, defined as Revised Cardiac Risk Index score = 3, scheduled for general anaesthesia. Fifty patients underwent baseline measurement of heart rate variability and were then assigned according to haemodynamic events (hypotension or bradycardia) after standardised induction of anaesthesia into 'stable' (n = 39) and 'unstable' patients (n = 11). Unstable patients had significantly lower baseline total power. Total power < 500 ms2 x Hz(-1) was associated with high sensitivity and specificity for the prediction of hypotension or bradycardia. Prospectively, 29 patients with total power < 500 ms2 x Hz(-1) were compared with 21 patients with total power > 500 ms2 x Hz(-1). Differences were found in the lowest mean arterial pressure and heart rate after induction of anaesthesia. We conclude that the pre-operative total power of heart rate variability in high risk patients may indicate the occurrence of haemodynamic events with high sensitivity and specificity. Heart rate variability may be a suitable tool to identify patients at high risk of a haemodynamic event and may be used to indicate need for intensive monitoring and, perhaps, prophylactic treatment.

Myocardial performance index during rapidly changing loading conditions: impact of different tidal ventilation.

BACKGROUND AND OBJECTIVES: The myocardial performance index is a non-geometric, heart rate-independent echocardiography-derived index of left ventricular performance combining systolic and diastolic function. There is an ongoing debate whether the myocardial performance index is affected by preload or not. Moreover, a systematic evaluation of the effect of changing tidal volume ventilation on the myocardial performance index is still lacking. The aim of our study was to assess whether acute changes in preload and/or different depth of tidal volume ventilation affect the myocardial performance index. METHODS: In all, 14 anesthetized pigs (35 +/- 2 kg) were studied during changing tidal volumes (VT 5, 10 and 15 mL kg(-1)) at baseline, after removal of 500 cm(3) of blood (haemorrhage) and after retransfusion of shed blood plus additional 500 cm(3) 6% hydroxyethyl starch (fluid loading). Echocardiographic measurements at each experimental stage included myocardial performance index, left ventricular end-diastolic area and fractional area change. Central venous pressure, pulmonary capillary wedge pressure, cardiac output and stroke volume index were obtained by a pulmonary artery catheter. Global end-diastolic volume was obtained by transpulmonary thermodilution. RESULTS: Comparing different loading conditions, we found significant changes in cardiac output, stroke volume index, central venous pressure, pulmonary capillary wedge pressure, global end diastolic volume and left ventricular end-diastolic area, indicating clinically relevant changes in preload. In the haemorrhage group, there was a significant reduction in the myocardial performance index (P < 0.05) independent of tidal volume applied and this was reversed after fluid loading. However, myocardial performance index was significantly impaired (P < 0.05) by high tidal volume ventilation (15 mL kg(-1)), while tidal volumes of 5 and 10 mL kg(-1) had no effect. CONCLUSIONS: The myocardial performance index is largely dependent on changes in preload. Moreover, high tidal volume ventilation significantly impaired the myocardial performance index.

Prevalidation of the ex-vivo model PCLS for prediction of respiratory toxicity.

In acute inhalation toxicity studies, animals inhale substances at given concentrations. Without additional information, however, appropriate starting concentrations for in-vivo inhalation studies are difficult to estimate. The goal of this project was the prevalidation of precision-cut lung slices (PCLS) as an ex-vivo alternative to reduce the number of animals used in inhalation toxicity studies. According to internationally agreed principles for Prevalidation Studies, the project was conducted in three independent laboratories. The German BfR provided consultancy in validation principles and independent support with biostatistics. In all laboratories, rat PCLS were prepared and exposed to 5 concentrations of 20 industrial chemicals under submerged culture conditions for 1h. After 23 h post-incubation, toxicity was assessed by measurement of released lactate dehydrogenase and mitochondrial activity. In addition, protein content and pro-inflammatory cytokine IL-1α were measured. For all endpoints IC50 values were calculated if feasible. For each endpoint test acceptance criteria were established. This report provides the final results for all 20 chemicals. More than 900 concentration-response curves were analyzed. Log10[IC50 (µM)], obtained for all assay endpoints, showed best intra- and inter-laboratory consistency for the data obtained by WST-1 and BCA assays. While WST-1 and LDH indicated toxic effects for the majority of substances, only some of the substances induced an increase in extracellular IL-1α. Two prediction models (two-group classification model, prediction of LC50 by IC50) were developed and showed promising results.

Fluconazole is removed by continuous venovenous hemofiltration in a liver transplant patient.

Fluconazole is effective for the treatment of fungal infections. A continuous venovenous hemofiltration (CVVH) was necessary in a liver transplant patient with anuria. Fluconazole treatment was started after the diagnosis of systemic candidiasis. There was no adverse effect on liver function, and the immunosuppression with cyclosporine was not affected. It is shown for the first time that CVVH effectively removes fluconazole from the blood circulation by a clearance into the hemofiltrate of approximately 21 ml/min. These data suggest that the treatment of fungal infections with fluconazole does not necessitate a reduction of the dosage during CVVH.

C1840-T mutation in the human skeletal muscle ryanodine receptor gene: frequency in northern German families susceptible to malignant hyperthermia and the relationship to in vitro contracture response.

In swine, a point mutation in the ryanodine receptor gene can account for all cases of malignant hyperthermia (MH). The frequency of a corresponding mutation in humans (C1840-T) and its relationship to the in vitro contracture profile is unknown. We screened 192 patients from 28 unrelated northern German families for the C1840-T mutation in the human ryanodine receptor gene and tested for MH susceptibility using the in vitro contracture test (IVCT) according to the European MH Protocol. In our patients 106 revealed MH susceptible (MHS), 56 MH nonsusceptible and 30 MH equivocal status following IVCT. In each family one or two individuals had developed clinical signs of MH or a MH crisis. All of these patients were classified MHS. The C1840-T mutation was found in 2 of 28 families (7.1%). All eight individuals of the two families characterized by this mutation revealed MHS status following IVCT. The thresholds for halothane- and caffeine-induced contractures as well as the contracture profiles following cumulative (0.4-10.0 mumol/l every 3 min) and bolus (10 mumol/l) administration of ryanodine were found to be similar in MHS patients with and without the C1840-T mutation. In conclusion, the C1840-T mutation in the human ryanodine receptor gene is a rare abnormality in MHS families. Similar contracture profiles in the presence and absence of this mutation might imply no major functional role with respect to the contracture response. At present, molecular genetic analysis cannot replace IVCT to discover MH susceptibility in humans.