Bleeding management with fibrinogen concentrate targeting a high-normal plasma fibrinogen level: a pilot study.

BACKGROUND: Bleeding diathesis after aortic valve operation and ascending aorta replacement (AV-AA) is managed with fresh-frozen plasma (FFP) and platelet concentrates. The aim was to compare haemostatic effects of conventional transfusion management and FIBTEM (thromboelastometry test)-guided fibrinogen concentrate administration. METHODS: A blood products transfusion algorithm was developed using retrospective data from 42 elective patients (Group A). Two units of platelet concentrate were transfused after cardiopulmonary bypass, followed by 4 u of FFP if bleeding persisted, if platelet count was < or =100 x 10(3) microl(-1) when removing the aortic clamp, and vice versa if platelet count was >100 x 10(3) microl(-1). The trigger for each therapy step was > or =60 g blood absorbed from the mediastinal wound area by dry swabs in 5 min. Assignment to two prospective groups was neither randomized nor blinded; Group B (n=5) was treated according to the algorithm, Group C (n=10) received fibrinogen concentrate (Haemocomplettan P/Riastap, CSL Behring, Marburg, Germany) before the algorithm-based therapy. RESULTS: A mean of 5.7 (0.7) g fibrinogen concentrate decreased blood loss to below the transfusion trigger level in all Group C patients. Group C had reduced transfusion [mean 0.7 (range 0-4) u vs 8.5 (5.3) in Group A and 8.2 (2.3) in Group B] and reduced postoperative bleeding [366 (199) ml vs 793 (560) in Group A and 716 (219) in Group B]. CONCLUSIONS: In this pilot study, FIBTEM-guided fibrinogen concentrate administration was associated with reduced transfusion requirements and 24 h postoperative bleeding in patients undergoing AV-AA.

Platelet concentrates transfusion in cardiac surgery and platelet function assessment by multiple electrode aggregometry.

BACKGROUND: Platelet dysfunction contributes to the pathophysiology of bleeding complications during and after cardiac surgery. In most surgical institutions, no peri-operative point-of-care monitoring of platelet function is used. We evaluated the usefulness of the Multiplate platelet function analyser based on impedance aggregometry for identifying groups of patients at a high risk of transfusion of platelet concentrates (PC). METHODS: Platelet function parameters were determined in 60 patients before and after routine cardiac surgery. Impedance aggregometry measurements were performed on Multiplate using ADP (ADPtest), collagen (COLtest) and thrombin receptor activating peptide (TRAPtest) as platelet activators. The correlations between the aggregometry results and the transfusion of PC were calculated. The results of the aggregation tests were also divided into tertiles and the differences in PC transfusion between the low and the high tertile were assessed. RESULTS: Low aggregometry delimited groups of patients with significantly higher PC transfusion. In the receiver operating characteristic curve, low pre-operative aggregation in the ADPtest identified patients with high total transfusion of PC (area under the curve 0.74, P=0.001), while the ADPtest performed at the end of the operation identified patients with high PC transfusion on the intensive care unit (ICU) (area under the curve 0.76, P=0.002). CONCLUSIONS: Near-patient platelet aggregation may allow the identification of patients with enhanced risk of PC transfusion, both pre-operatively and upon arrival on the ICU.

Comparison of breathing tube connectors during invasive bronchial procedures.

Bronchoscopy and bronchial suctioning during intra-operative artificial ventilation often causes leakage from the ventilation circuit with a decrease in ventilatory parameters and possible workplace contamination with anaesthetic gases. Different connectors have been developed to reduce gas leakage. We evaluated the following connectors : VBM 2 mm, 3 mm and 5 mm, Bodai Suction-Safe, Bodai Bronch-Safe and Bodai Trach-Safe, as well as the BE 105-7, BE 105-8 and SH 7-45. Invasive bronchial instruments (catheters, bronchoscopes and bronchial blockers) with 1.67-7.33 mm diameter were used. Pressure-controlled ventilation was performed on a test lung using a ventilator. Sevoflurane concentration in the room was measured 0.2 and 1.5 m from the connector using a photo-acoustic infrared-spectroscope. The VBM connectors caused the least gas leak and ensured stability of ventilation parameters even at peak pressures when combined with smaller instruments. With instruments > 6 mm, BE 105-7, BE 105-8 and SH 7-45 connectors performed best. The Bodai connectors showed a reduced ability to prevent leakage and to keep ventilatory parameters stable. All connectors, excluding the Bodai Trach-Safe, prevented exposure to anaesthetic gases beyond the current safety recommendations when combined with the fitting instruments. The connectors showed different ranges of tightness, equivalent to different ranges of compatibility with the instruments used.

Role of endotoxin in the pathogenesis of critical illness polyneuropathy.

Critical illness polyneuropathy (CIP) occurs in association with sepsis and multiple organ failure; however, little is known about the pathomechanisms of CIP and its therapy. In order to determine the parameters which interfere with development of CIP, electrophysiological investigations of peripheral nerves and biochemical measures were correlated to each other. The present study includes 20 consecutive patients in an intensive care unit developing severe sepsis or septic shock. Nerve conduction studies and electromyography were performed with occurring sepsis (day 1, 7, 14) and neurophysiological parameters were correlated with biochemical measures, especially indicators of infection and inflammation. It was found that all patients developed neurophysiological signs of axonal motor polyneuropathy. There was a significant correlation between serum concentrations of endotoxin and interleukin-2 receptors (IL2-R) and reduction of the amplitude of the compound motor action potentials. Other clinical and biochemical parameters showed no significant correlations with neurophysiological data. This finding apparently indicates that endotoxin damages nerve axons directly or indirectly, e.g. by activation of inflammatory cascades (IL2-R). Endotoxin appears to be an essential factor in the pathogenesis of CIP in sepsis, and therapeutic options neutralizing endotoxin may prevent development of CIP.

Endocrine stress response and inflammatory activation during CABG surgery. A randomized trial comparing remifentanil infusion to intermittent fentanyl.

BACKGROUND AND OBJECTIVE: Our aim was to compare a continuous infusion of remifentanil with intermittent boluses of fentanyl as regards the perioperative hormonal stress response and inflammatory activation in coronary artery bypass graft patients under sevoflurane-based anaesthesia. METHODS: In all, 42 patients undergoing coronary artery bypass grafting with cardiopulmonary bypass were prospectively randomized to a fentanyl group (n = 21, total fentanyl dose 2.6 +/- 0.3 mg), or a remifentanil group (n = 21, infusion rate 0.25 microg kg(-1) min(-1)). Haemodynamics, plasma levels of epinephrine, norepinephrine, antidiuretic hormone, adrenocorticotropic hormone, cortisol, complement activation (C3a, C5b-9), interleukin (IL)-6, IL-8 and tumour necrosis factor-alpha were measured at T1: baseline, T2: intubation, T3: sternotomy, T4: 30 min on cardiopulmonary bypass, T5: end of surgery and T6: 8 h postoperatively. Troponin T and creatine kinase-MB were measured postoperatively. RESULTS: Patients in the remifentanil group were extubated significantly earlier than fentanyl patients (240 +/- 182 min vs. 418 +/- 212 min, P = 0.006). Stress hormones 30 min after start of cardiopulmonary bypass showed higher values in the fentanyl group compared to the remifentanil group (antidiuretic hormone (ADH): 39.94 +/- 30.98 vs. 11.7 +/- 22.8 pg mL(-1), P = 0.002; adrenocorticotropic hormone: 111.5 +/- 116.8 vs. 21.81 +/- 24.71 pg mL(-1), P = 0.01; cortisol 185 +/- 86 vs. 131 +/- 82 ng mL(-1), P = 0.04). The interleukins were significantly higher at some perioperative time points in the fentanyl group compared to the remifentanil group (tumour necrosis factor: T5: 3.57 vs. 2.37; IL-6: T5: 4.62 vs. 3.73; and IL-8: T5: 4.43 vs. 2.65 and T6: 2.61 vs. 1.13). However, cardiopulmonary bypass times and aortic cross-clamp times were longer in the fentanyl group, which may to some extent account for the differences. CONCLUSIONS: The perioperative endocrine stress response was attenuated in patients supplemented with continuous remifentanil infusion as compared to intermittent fentanyl.

[Are there pulmonary vascular or respiratory effects of prostaglandin vehicles (ethanol, glycine buffer) after intravenous infusion or inhalation?]. / Verursacht die Infusion oder Inhalation von Prostaglandin-Trägerlösungen (Athanol, Glycin-Puffer) pulmonalvaskuläre oder respiratorische Effekte?

BACKGROUND: Infusion or inhalation of prostaglandins PGE1 and PGI2 is used to reduce vascular resistance. PGE1 and PGI2 are dissolved in ethanol and glycine buffer, respectively. Each vehicle may cause dose-dependent haemodynamic and respiratory side effects. This study was performed to examine the role of low-dose ethanol and glycine buffer as used for the infusion and inhalation of PGE1 and PGI2. METHODS: Two groups of pigs (ethanol and glycine group, n = 9 each) were anaesthetised and ventilated mechanically. Ethanol was given at 0.14 mg/kg/min by infusion and 0.12 mg/kg/min as aerosol, glycine buffer was infused at 3.8 microg/kg/min and inhaled at 3.1 microg/kg/min, respectively. Haemodynamic and respiratory data were recorded before and after application. RESULTS: Neither infusion nor inhalation of ethanol or glycine buffer caused significant changes in systemic and pulmonary haemodynamics, right heart function, oxygenation or ventilation. CONCLUSIONS: The effect of inhaled or intravenously infused PGE1 and PGI2 is not influenced by their preparations containing ethanol or glycine buffer.

[Evaluation of blood and breath alcohol measurement in patients with hepatocellular carcinoma during procedures in intubated patients with percutaneous ethanol instillation]. / Vergleich von Blut- und Atemalkoholkonzentrationen während der perkutanen Athanolinstillationstherapie (PEIT) bei intubierten Patienten mit hepatozellulärem Karzinom.

The accuracy of breath alcohol measurements in intubated patients with assisted ventilation was evaluated. The breath alcohol concentration was measured in 24 patients undergoing percutaneous alcohol injection therapy for hepatocellular carcinoma with Alcotest 7410 med, from Dräger, Germany. The blood ethanol concentrations (BACs) were determined in each blood serum applying the German forensic criteria standard, namely, two alcohol dehydrogenase (ADH) and two gas chromatography (GC) measurements. The blood alcohol concentrations were between 0.07 and 1.51 per thousand in the central venous samples and 0.02-1.66 per thousand in the arterial samples. An excellent correlation between both the venous and arterial blood alcohol concentrations (r2=0.94), as well as between the breath alcohol concentrations and the venous (r2=0.84) or arterial alcohol concentration (r2=0.89), p<0.01 for both parameters was revealed. Determination of breath alcohol concentration using the Alcotest in intubated patients is reliable and reflects the blood alcohol values.

Postoperative nausea and vomiting (PONV) : usefulness of the Apfel-score for identification of high risk patients for PONV.

OBJECTIVE: Postoperative nausea and vomiting (PONV) still represent an important problem in surgery. Treatment and prevention of PONV requires accurate risk stratification. The simplified Apfel-score includes the four factors female gender, no smoking, postoperative use of opioides and previous PONV or motion-sickness in patients' history. Each of these risk factors is supposed to elevate the PONV-incidence about 20%. The aim of the study was to validate this clinical risk assessment score in patients with high risk for PONV. METHODS: In a prospective study 93 patients with high risk preoperative score for PONV (Apfel Score III and IV) were analyzed. Patients and nurses were interviewed using a standardized questionnaire at the time of discharge from the post-anesthesia care unit (PACU) as well as 6 hours and 24 hours after admission to the PACU. General anaesthesia was applied as total intravenous anaesthesia (TIVA) with mivacurium, propofol and remifentanil (no nitrous oxide / FI 02 0.5) RESULTS: In the group with Apfel score III PONV occurred in 59.7% of patients and in the Apfel score group IV in 91.3% of all patients. The incidence of PONV corresponds to the predicted values of 60% for Apfel III and 80% for Apfel IV although the use of TIVA should have reduced the incidence of PONV about 26%. This apparent overestimation could be explained by the frequent questioning of patients and nurses for PONV leading to assessment of very minor symptoms. CONCLUSION: The Apfel-score is a useful and simple tool for stratification of patients with high risk for PONV.

[Assessment of anesthesia methods in ophthalmologic surgery by patients, surgeons, and anesthesiologists]. / Bewertung von Narkoseverfahren in der Ophthalmochirurgie durch Patienten, Operateur und Anästhesisten.

BACKGROUND: The purpose of this study was to evaluate anesthesia methods in ophthalmic surgery in elderly people assessed by patients, surgeon, and anesthesiologist using subjective rating scales. PATIENTS AND METHODS: In a prospective, randomized study we compared in 52 (26 vs 26) elderly patients (ASA II and III, mean age 78.7+/-8.6 years) undergoing a cataract operation the satisfaction perceived by patients, surgeons, and anesthesiologists in relation to anesthesia methods [intravenous anesthesia (TIVA) vs balanced anesthesia (BA)] based on a score from 1=best to 6=worse. RESULTS: Patient satisfaction was better in the TIVA group (1.65) than in the patients treated with BA (2.57), p<0.001. Surgeons perceived no difference (BA 1.15/TIVA 1.07). Anesthesiologists preferred TIVA (TIVA 1.5/BA 3.23), p<0.001. CONCLUSION: In this study patients and anesthesiologists preferred TIVA. There was no difference between TIVA and BA as seen by the surgeon.

Hemodynamic consequences of porcine kidney xenograft reperfusion in cynomolgus monkeys.

BACKGROUND: After xenograft reperfusion, complement activation may lead to generation of anaphylatoxins and cardiocirculatory instability of the recipient. METHODS: In 13 cynomolgus recipients of either unmodified or human decay accelerating factor transgenic porcine kidneys cardiocirculatory parameters were measured by single indicator transpulmonary thermodilution. RESULTS: After graft reperfusion, recipient cardiac output decreased by 25.4% (P<0.05), intrathoracic blood volume by 22.8% (P<0.05), extravascular lung water increased slightly (P=n.s.). The impairment in cardiac output was neither influenced by the graft's weight or human decay accelerating factor transgenicity. sC3a and sC5b-9 complement levels in the recipient monkeys showed a sharp peak upon reperfusion. CONCLUSIONS: After reperfusion a marked and significant cardiodepression accompanied by relative volume depletion were observed. Analysis of volume status ruled out a mere volume shift as the underlying reason for the observed drop in cardiac output. These data may be relevant for the perioperative management of human recipients of discordant xenografts in the future.

Influence of cold ischemia time, pretransplant anti-porcine antibodies, and donor/recipient size matching on hyperacute graft rejection after discordant porcine to cynomolgus kidney transplantation.

Organs transplanted between phylogenetically disparate species, such as from the pig into the primate, are subject to hyperacute rejection (HAR). This form of xenograft rejection is mediated by preformed natural antibodies and is believed to occur invariably in discordant xenografts thus leading to rapid destruction and complete thrombosis of the graft. Recent data, however, have shown that in the porcine to cynomolgus monkey setting, HAR is not inevitably seen after porcine kidney transplantation. The influence of preoperative antiporcine antibody levels in the recipient, cold ischemia time, and donor organ weight on the onset of HAR was investigated by using unmodified large white pigs (aged 3-12 weeks) as organ donors and adult cynomolgus monkeys (aged 1.5-3.5 years) as recipients. Porcine kidney xenotransplantation was performed in either a non-life-supporting model (n=7) or in a life-supporting model (n=8). In both models, no correlation was found between cold ischemia time and HAR. When preoperative anti-porcine antibody levels were investigated, a significant increase in incidence of HAR was observed in animals with elevated anti-porcine IgM (P<0.05) but not IgG levels (P=NS). Interestingly, although 5 of 12 grafts with an organ weight of less than 50 g underwent HAR, none of three grafts with a donor organ weight of more than 70 g showed signs of HAR. In addition, all three larger grafts showed intraoperative and postoperative urine production, although only in 1 (48 g) of the 12 grafts weighing less than 50 g primary graft function was observed. In one animal, a second porcine kidney (23 g) was successfully transplanted (without HAR) immediately after HAR and subsequent removal of a first porcine kidney (20 g). These results indicate that in the porcine to cynomolgus monkey setting anti-porcine IgM rather than IgG anti-porcine antibody levels seem to be of predominant importance for the induction of HAR. By increasing the donor organ size and weight the frequency of the onset of HAR can be at least reduced. This is most likely due to immunoabsorption of the recipients preformed antibodies in the porcine kidney without lethal damage for the graft.

Voltage-dependent block of normal and mutant muscle sodium channels by 4-Chloro-m-Cresol.

1 The effects of 4-Chloro-m-Cresol (4-CmC) were examined on heterologously expressed wild type (WT), Paramyotonia Congenita (R1448H) and Hyperkalemic Periodic Paralysis (M1360V) mutant alpha-subunits of human muscle sodium channels. 2 Block of rested sodium channels caused by 4-CmC was concentration-dependent with an ECR50 of 0.40 mM in WT, 0.45 mM in R1448H and 0.49 mM in M1360V. 3 Inactivation significantly promoted 4-CmC-induced sodium channel block in all clones indicated by 4-CmC-induced shifts of steady-state availability curves, reflecting a higher proportion of channel block at depolarized membrane potentials. Channel block was almost complete (>90%) at concentrations close to the ECR50 (0.5 mM) on application of an inactivating prepulse before the test pulse. 4 4-CmC accelerated the current decay following depolarization and prolonged recovery from inactivation in all clones. Of these, R1448H, the mutant which displayed severely impaired inactivation in the controls, responded to 4-CmC with the most pronounced acceleration of inactivation. Control experiments revealed enhanced recovery from inactivation in the mutants, which was restored to normal in 0.1 mM 4-CmC. 5 4-CmC induced no additional frequency-dependent block. 6 Our results clearly demonstrate that 4-CmC is as effective as lidocaine (Fan et al., 1996) in blocking muscle sodium channels. Low concentrations of the compound (

Structural requirements for voltage-dependent block of muscle sodium channels by phenol derivatives.

We have studied the effects of four different phenol derivatives, with methyl and halogen substituents, on heterologously expressed human skeletal muscle sodium channels, in order to find structural determinants of blocking potency. All compounds blocked skeletal muscle sodium channels in a concentration-dependent manner. The methylated phenol 3-methylphenol and the halogenated phenol 4-chlorophenol blocked sodium currents on depolarization from -100 mV to 0 mV with IC(50) values of 2161 and 666 microM respectively. Methylation of the halogenated compound further increased potency, reducing the IC(50) to 268 microM in 2-methyl-4-chlorophenol and to 150 microM in 3,5-dimethyl-4-chlorophenol. Membrane depolarization before the test depolarization increased sodium channel blockade. When depolarizations were started from -70 mV or when a 2.5 s prepulse was introduced before the test pulse inducing slow inactivation, the IC(50) was reduced more than 3 fold in all compounds. The values of K(D) for the fast-inactivated state derived from drug-induced shifts in steady-state availability curves were 14 microM for 3,5-dimethyl-4-chlorophenol, 19 microM for 2-methyl-4-chlorophenol, 26 microM for 4-chlorophenol and 115 microM for 3-methylphenol. All compounds accelerated the current decay during depolarization and slowed recovery from fast inactivation. No relevant frequency-dependent block after depolarizing pulses applied at 10, 50 and 100 Hz was detected for any of the compounds. All the phenol derivatives that we examined are effective blockers of skeletal muscle sodium channels, especially in conditions that are associated with membrane depolarization. Blocking potency is increased by halogenation and by methylation with increasing numbers of methyl groups.

Voltage-dependent blockade of normal and mutant muscle sodium channels by benzylalcohol.

1. We studied the effects of benzylalcohol on heterologously expressed wild type (WT), paramyotonia congenita (R1448H) and hyperkalaemic periodic paralysis (M1360V) mutant alpha-subunits of human skeletal muscle sodium channels. 2. Benzylalcohol blocked rested channels at -150 mV membrane potential, with an ECR(50) of 5.3 mM in wild type, 5.1 mM in R1448H, and 6.2 mM in M1360V. When blockade was assessed at -100 mV, the ECR(50) was reduced in R1448H (2 mM) compared with both wild type (4.3 mM; P<0.01) and M1360V (4.3 mM). 3. Membrane depolarization before the test depolarization significantly promoted benzylalcohol-induced sodium channel blockade. The values of K(D) for the fast-inactivated state derived from benzylalcohol-induced shifts in steady-state availability curves were 0.66 mM in wild type and 0.58 mM in R1448H. In the presence of slow inactivation induced by 2.5 s depolarizing prepulses, the ECI(50) for benzylalcohol-induced current inhibition was 0.59 mM in wild type and 0.53 mM in R1448H. 4. Recovery from fast inactivation was prolonged in the presence of drug in all clones. 5. Benzylalcohol induced significant frequency-dependent block at stimulating frequencies of 10, 50, and 100 Hz in all clones. 6. Our results clearly show that benzylalcohol is an effective blocker of muscle sodium channels in conditions that are associated with membrane depolarization. Mutants that enter voltage-dependent inactivation at more hyperpolarized membrane potentials compared with wild type are more sensitive to inhibitory effects at the normal resting potential.

Changes in hemodynamic parameters, inotropic state, and myocardial oxygen consumption owing to intravenous application of nitroglycerin.

Changes in hemodynamics, inotropic state, and myocardial oxygen consumptom were investigated in a total of 70 patients with coronary disease after intravenous application of nitroglycerin (0.4 mg., 0.2 mg., and 2 mg. per hour). The results demonstrate that nitroglycerin enlarges therapeutic possibilities during and immediately after operations in patients with limited coronary reserve. The decrease in myocardial oxygen consumption, dependent on dose, ranged between 15.8 and 22.9 per cent.

Massive doses of methylprednisolone (30 mg/kg) in man: immediate haemodynamic effects in "low output state".

Methylprednisolone, 30 mg/kg body weight, was given as an intravenous bolus injection to a total of 31 cardiosurgical patients. Measurements of left ventricular parameters showed no significant increase in dp/dtmax and no significant decrease in left ventricular end-diastolic pressure. There were no important changes in blood pressure, heart rate, cardiac index, stroke index and total peripheral resistance. During 'steady state' extracorporeal circulation no relevant vasodilating effect could be found. In comparison to a control-group there were no important differences in haemodynamic parameters. In cardio-surgical patients, --mainly functional class III--we were unable to demonstrate any gross cardiovascular effects of large doses of methylprednisolone.

Standard calculation of ethanol elimination rate is not sufficient to provide ethanol substitution therapy in the postoperative course of alcohol-dependent patients.

OBJECTIVE: Alcohol withdrawal syndrome (AWS) is a severe complication during postoperative treatment of alcohol-dependent patients. Besides the use of clomethiazole, clonidine, and benzodiazepines, there is another possible way to prevent AWS by deliberate administration of ethanol. The appropriate dosage of ethanol has not been known up to now and it could be defined according to the average ethanol elimination rate (EER) which, from forensic analysis, is known to be 15 mg/dl per h in a normal population. However, it is questionable whether these data are suitable for the calculation of the correct dosage in alcohol-dependent patients. DESIGN: Preliminary retrospective descriptive study. SETTING: Intensive care unit of a university teaching hospital. PATIENTS: 11 alcohol-dependent patients (9 males, 2 females, mean age 50.8 years, range 33 to 60 years). INTERVENTIONS: Ethanol substitution (ES) by parenteral application. MEASUREMENTS AND RESULTS: Ethanol kinetics were evaluated by repeated measurement of the blood ethanol concentration (BEC) over a period of at least 6 h parallel to the administration of ethanol. The average EER was found to be 28 mg/dl per h with a standard deviation of 11 mg/ dl per h. The minimum value was 18 mg/dl per h and the maximum 50 mg/dl per h. These EERs were significantly higher than the EERs known from forensic analysis. AWS was prevented in all 11 patients. CONCLUSIONS: Close control of BEC and precise adjustment of ethanol administration are necessary prerequisites for ES. The standard EER is not sufficient to define the appropriate ethanol dosage due to enormous variations in the ethanol metabolism of alcohol-dependent patients.

Predictors of respiratory function deterioration after transfer of critically ill patients.

OBJECTIVES: Critically ill patients are often transferred due to the growing number of diagnostic procedures required to be performed outside the intensive care unit. These transfers have proved to be very critical. The aim of this study was to evaluate predictors for the deterioration of respiratory function in critically ill patients after transfer. DESIGN: Prospective, clinical, observational study. SETTING: 1800-bed university teaching hospital. SUBJECTS: 98 mechanically ventilated patients were investigated during transfer. MEASUREMENT AND MAIN RESULTS: Before transfer, all patients were classified according to the Acute Physiology and Chronic Health Evaluation (APACHE) II score and the Therapeutic Intervention Scoring System (TISS). Haemodynamics and arterial blood gases were measured at 11 different times. Arterial oxygen tension (PaO2), fractional inspired oxygen (FIO2), PaO2/FIO2 ratio, lowest PaO2/FIO2 ratio, minimal PaO2 and maximal FIO2, APACHE II score, TISS before transfer, age and duration of transfer were analysed as potential predictors for deterioration of respiratory function after transfer. Variables were analysed using Classification and Regression Trees and Clustering by Response. In 54 transports (55%) there was a decrease in the PaO2/FIO2 ratio, and a decrease of more than 20% from baseline was noted in 23 of the transferred patients (24%). Age > 43 years and FIO2 > 0.5 were identified as predictors for respiratory deterioration. CONCLUSIONS: Our predictors were able to indicate deterioration after transfer correctly in 20 of 22 patients (91%), combined with a false-positive rate in 17 of 49 (35%).

Septic shock after liver transplantation for Caroli's disease: clinical improvement after treatment with C1-esterase inhibitor.

The extent of complement and contact activation is related to outcome in sepsis. A low functional index of their main blocker C1-esterase inhibitor (C1-INH) is considered as a relative deficiency of C1-INH and might contribute to the development of fatal complications in the intensive care unit. The first results of therapeutic intervention with C1-INH concentrate in septic shock are promising. We report on our experience of C1-INH concentrate administration in a young woman with Caroli's disease as ultimate rescue therapy for septic shock with capillary leakage syndrome after combined liver and kidney transplantation. No focus of infection was detectable and thus surgical intervention was not indicated. Antibiotic therapy at that time included vancomycin, tobramycin, meropenem and fluconazol. Hemodynamic stabilization occurred within hours after administration of C1-INH concentrate. Simultaneously a reduction in vasopressor medication was possible and negative fluid balance was achieved.

Phenol derivatives accelerate inactivation kinetics in one inactivation-deficient mutant human skeletal muscle Na(+) channel.

Altered inactivation kinetics in skeletal muscle Na(+) channels due to mutations in the encoding gene are causal for the alterations in muscle excitability in nondystrophic myotonia. Na(+) channel blockers like lidocaine and mexiletine, suggested for therapy of myotonia, do not reconstitute inactivation in channels with defective inactivation in vitro. We examined the effects of four methylated and/or halogenated phenol derivatives on one heterologously expressed inactivation-deficient Paramyotonia congenita-mutant (R1448H) muscle Na(+) channel in vitro. All these compounds accelerated delayed inactivation of R1448H-whole-cell currents during a depolarization and delayed accelerated recovery from inactivation. The potency of these effects paralleled the potency of the drugs to block the peak current amplitude. We conclude that the investigated phenol derivatives affect inactivation-deficient Na(+) channels more specifically than lidocaine and mexiletine. However, for all compounds, the effect on inactivation was accompanied by a substantial block of the peak current amplitude.