[Functioning of the anaesthetic conserving device: aspects to consider for use in inhalational sedation]. / Funktionsweise des "Anaesthetic Conserving Device" : Besonderheiten beim Einsatz zur inhalativen Sedierung.

The new anaesthetic conserving device (ACD) allows the use of isoflurane and sevoflurane without classical anaesthesia workstations. Volatile anaesthetic exhaled by the patient is absorbed by a reflector and released to the patient during the next inspiration. Liquid anaesthetic is delivered via a syringe pump. Currently the use of the ACD is spreading among European intensive care units (ICU). This article focuses on the functioning of the device and on particularities which are important to consider. The ACD constantly reflects 90% of the exhaled anaesthetic back to the patient, but if one exhaled breath contains more than 10 ml of anaesthetic vapour (e.g. >1 vol% in 1,000 ml), the capacity of the reflector will be exceeded and relatively more anaesthetic will be lost to the patient. This spill over decreases efficiency but it also contributes to safety as very high concentrations are averted. Compared to classical anaesthesia systems the ACD used in conjunction with ICU ventilators offers advantages in the ICU setting: investment costs are low, carbon dioxide absorbent is not needed, breathing comfort is higher, anaesthetic consumption is low (equal to an anaesthesia circuit with a fresh gas flow of approximately 1 l/min) and anaesthetic concentrations can be controlled very quickly (increased by small boluses and decreased by removal of the ACD). On the other hand, case costs are higher (single patient use) and a dead space of 100 ml is added. There are pitfalls: by a process called auto-pumping, expansion of bubbles inside the syringe may lead to uncontrolled anaesthetic delivery. Auto-pumping is provoked by high positioning of the syringe pump, heat and prior cooling of the liquid anaesthetic. Inherent to the device is an early inspiratory concentration peak and an end-inspiratory dip which may mislead commonly used gas monitors. Workplace concentrations can be minimized by proper handling, a sufficient turnover of room air is important and gas from the expiration port of the ventilator should be scavenged. Inhalational compared to intravenous ICU sedation offers the advantages of better control of the sedation level, online drug monitoring, no accumulation in patients with renal or hepatic insufficiency and bronchodilation. With a lowered opioid dose spontaneous breathing and intestinal motility are well preserved. A clinical algorithm for the care of patients with respiratory insufficiency including inhalational sedation is proposed. Inhalational sedation with isoflurane has been widely used for more than 20 years in many countries and even for periods of up to several weeks. In the German S3 guidelines for the management of analgesia, sedation and delirium in intensive care (Martin et al. 2010), inhalational sedation is mentioned as an alternative sedation method for patients ventilated via an endotracheal tube or a tracheal cannula. Nevertheless, isoflurane is not officially licensed for ICU sedation and its use is under the responsibility of the prescribing physician.

[The design of the VISEP trial. Critical appraisal]. / Studienprotokoll der VISEP-Studie. Eine kritische Stellungnahme.

The survey transcript of the VISEP interventional trial "Prospective randomized multicenter study on the influence of colloid vs crystalloid volume resuscitation and of intensive vs conventional insulin therapy on outcome in patients with severe sepsis and septic shock" [Clinical trials.gov. identifier: NCT00135473; study start April 2003] comprises, according to the data of the year 2003, methodological shortcomings which challenge a priori the study design and thus the resolution of the purpose of the study, i.e., "determination of the influence of the studied volume and insulin interventions on morbidity and mortality of patients with severe sepsis and septic shock". The most important points of criticism are: 1. A volume therapy with exclusively crystalloids or colloids with the chosen colloid hyperoncotic, hyperchloremic HES solution (10% hydroxyethyl starch: 10% Hemohes) or the crystalloid solution with high lactate content (Sterofundin) is neither acceptable nor practicable, even if only due to exceeding the maximum dosage as recommended by the manufacturer. 2. The fact known since the year 2001 that high molecular weight, poorly biodegradable HES preparations can present an independent risk-factor for acute kidney failure in patients with sepsis or septic shock was ignored: the exclusion criterion of a serum-creatinine value of >320 micromol/l (>3.6 mg/dl) was doubled in relation to the manufacturer's specification. 3. The hyperoncotic colloid solution used (10% Hemohes) may only be employed for a brief period: it is highly hyperchloremic and causes extravascular hypohydration with consecutive reduction of renal excretion, which together with HES is a fatal combination. 4. The crystalloid solution used, i.e., Sterofundin, which contains 45 mmol/l lactate, is contraindicated with septic shock as it increases the patient's O2 consumption, hinders lactate diagnostics as a hypoxia marker by simultaneous lactate infusion, and through increased gluconeogenesis leads to hyperglycemia, at least with diabetics. 5. It is doubtful whether an intensified insulin therapy (Actrapid) can be successful if insulin is administered simultaneously with iatrogenic hyperglycemia as a result of lactate influx. Due to these flaws in the design of the VISEP trial, the only consequence can be that the results of the survey are unusable, especially with regard to the point "HES and kidney function". Thus, any further advance presentations and interpretations should be shelved in expectation of the authors' publication of all the data, in order to begin further discussions including the flaws in study design listed here.

Desflurane compared with propofol for postoperative sedation in the intensive care unit.

BACKGROUND: We hypothesized that emergence from sedation in postoperative patients in the intensive care unit would be faster and more predictable after sedation with desflurane than with propofol. METHODS: Sixty patients after major operations were allocated randomly to receive either desflurane or propofol. The target level of sedation was defined by a bispectral index(TM) (BIS(TM)) of 60. All patients were receiving mechanical ventilation of the lungs for 10.6 (SD 5.5) h depending on their clinical state. The study drugs were stopped abruptly in a calm atmosphere with the fresh gas flow set to 6 litres min(-1), and the time until the BIS increased above 75 was measured (t(BIS75), the main objective measure). After extubation of the trachea, when the patients could state their birth date, they were asked to memorize five words. RESULTS: Emergence times were shorter (P<0.001) after desflurane than after propofol (25th, 50th and 75th percentiles): t(BIS75), 3.0, 4.5 and 5.8 vs 5.2, 7.7 and 10.3 min; time to first response, 3.7, 5.0 and 5.7 vs 6.9, 8.6 and 10.7 min; time to eyes open, 4.7, 5.7 and 8.0 vs 7.3, 10.5 and 20.8 min; time to squeeze hand, 5.1, 6.5 and 10.2 vs 9.2, 11.1 and 21.1 min; time to tracheal extubation, 5.8, 7.7 and 10.0 vs 9.7, 13.5 and 18.9 min; time to saying their birth date, 7.7, 10.5 and 15.5 vs 13.0, 19.4 and 31.8 min. Patients who received desflurane recalled significantly more of the five words. We did not observe major side-effects and there were no haemodynamic or laboratory changes except for a more marked increase in systolic blood pressure after stopping desflurane. Using a low fresh gas flow (air/oxygen 1 litre min(-1)), pure drug costs were lower for desflurane than for propofol (95 vs 171 Euros day(-1)). CONCLUSIONS: We found shorter and more predictable emergence times and quicker mental recovery after short-term postoperative sedation with desflurane compared with propofol. Desflurane allows precise timing of extubation, shortening the time during which the patient needs very close attention.

Tissue deposits of hydroxyethyl starch (HES): dose-dependent and time-related.

Tissue deposits occur after administration of plasma substitutes. After hydroxyethyl starch (HES), deposits may last for months, causing pruritus and impairment of function. Because elimination of HES deposits has not been demonstrated in humans, we studied 26 patients, for up to 7 yr after HES administration, to assess HES storage. HES dose ranged from 0.34 to 15.00 g kg-1 body weight, and administration intervals from 1 day to 7 yr. Biopsies of the liver, muscle, spleen, intestine or skin were studied using light and electron microscopy and immunohistochemistry. HES storage was dose-dependent, decreased in all organs with time and was greater in patients suffering from pruritus. We conclude that tissue deposition of HES is transitory and dose-dependent, with differences between subjects in severity and duration.

Hydroxyethyl starch antibodies in humans: incidence and clinical relevance.

UNLABELLED: Hydroxyethyl starch (HES) is a plasma expander used for perioperative i.v. fluid management, as well as for resuscitation from trauma and shock. HES is very well tolerated, and the incidence of anaphylactic reactions is lower than with dextran or gelatin. Dextran anaphylaxis is caused by circulating dextran-reactive antibodies (ABs) of the immunoglobin G (IgG) class found in most adults. Histamine release from mast cells induces adverse reactions after gelatin infusion. The cause of adverse reactions due to HES is not yet clear. To investigate AB formation due to HES, we collected sera of 1004 patients at least 14 days after starch administration. Using a highly sensitive enzyme-linked immunoabsorbent assay technique, we found one patient with a low 1:10 titer of HES-reactive ABs (immunoglobin M [IgM] class). Despite repeated HES infusions, no clinical reaction could be detected in this patient. On the basis of a binomial distribution, a one-tailed confidence interval (99%) was used to calculate the percentage of the occurrence of ABs in general with maximum of 33 in 10,000 persons (IgM) and 23 in 10,000 persons (IgG). We suggest that HES-reactive ABs are extremely rare and that they do not necessarily induce anaphylaxis. Other mechanisms may be responsible for adverse reactions due to HES. IMPLICATIONS: The frequency of antibody formation due to hydroxyethyl starch, a commonly used plasma expander, was prospectively investigated in 1004 patients. Only one patient showed transient antibody formation, which was not harmful to the patient. This low antigenicity could explain the excellent tolerance of hydroxyethyl starch compared with other plasma expanders.

[Effect of colloidal plasma substitutes on liberation of tumor necrosis factor-alpha (TNF-alpha) in human whole blood in vitro]. / Der Einfluss kolloidaler Plasmaersatzmittel auf die Freisetzung von Tumor-Nekrose-Faktor-alpha (TNF-alpha) in menschlichen Vollblut in vitro.

OBJECTIVE: To investigate the influence of colloidal plasma substitutes on human cytokine network, especially of tumor necrosis factor alpha (TNF-alpha), in vitro. DESIGN: Heparinized whole blood samples from 8 healthy volunteers were divided and set on various concentrations of artificial colloidal plasma substitutes (native = 0 mg/ml; 5 mg/ml; 15 mg/ml). As colloids were used hydroxyethyl starch 200/0.5 (HES), dextran 60 (DX), urea-linked gelatin (GEL) and human albumin solution (HA). After incubation (24 h; 5% CO2; 37 degrees C; with and without concomitant stimulation of blood cells with phytohemagglutinin [PHA]) measurement of TNF-alpha release was performed via ELISA by the method described by Gallati. For the statistical evaluation a repeated measures analysis of variance was used. RESULTS: Basic level of TNF-alpha was found between 226 and 273 pg/ml (0 mg of each colloid/ml), stimulation with PHA without any colloid increased the TNF-alpha level about fourfold (1,066-1,260 pg/ml; 0 mg of each colloid/ml). At 5 mg/ml and 15 mg/ml without PHA all 3 artificial colloids rose the level of TNF-alpha (up to 50%). Under concomitant stimulation each colloid induced additional TNF-alpha release in comparison to PHA alone. The changes elicited by DX and GEL were statistically significant (p < 0.001 and p = 0.005, respectively) in contrast to those induced by human albumin solution or HES. CONCLUSION: In relation to TNF-alpha plasma substitutes are not inert substances as perhaps suspected. The questions whether the observed effects exist in vivo how far other cytokines are influenced and the question about the clinical importance are subject of ongoing studies.

Wernicke's encephalopathy--causes to consider.

Wernicke's encephalopathy (WE) is a thiamine deficiency disorder and is characterized clinically by the triad of ocular abnormalities, ataxia and disturbances of consciousness. We report on 3 patients with WE, of whom 2 had insufficient thiamine substitution. In the first patient symptoms disappeared during thiamine substitution. In the second patient acute WE was the terminating event in the sequence of parenteral nutrition, lactic acidosis and cardio-pulmonary decompensation. Possibly due to hereditary deficits WE developed in the third patient despite sufficient thiamine substitution. Attention to thiamine deficiency should be paid in all patients with history of alcoholism, malnutrition, malabsorption, tumors, inflammation, other severe diseases and in parenteral hyperalimentation. In order to prevent WE thiamine should be substituted with at least 100 mg/day i.v. or i.m.

No evidence for the existence of preformed antibodies against hydroxyethyl starch in man.

Using the highly sensitive ELISA technique for detecting anti-hydroxyethyl starch (HES) antibodies in man sera from 1,056 patients were analyzed. Patients of both sex, who had never had any prior contact with HES, were included in the study. In none of the cases could any titer of HES-reactive antibodies be detected. These data suggest that in man preformed HES-reactive antibodies do not exist or are extremely rare. In any case, unlike dextran-reactive antibodies, they should not have a high clinical importance. The mechanism behind the very rarely observed anaphylactoid reactions after HES application is still unknown.

Oxalate-induced encephalitis after infusions of sugar surrogates.

The case of a 55-year-old female with oxalate-induced lethal encephalitis following infusions of sugar surrogates is reported. Renal failure and subsequent central coma developed following the use of xylitol, fructose and sorbitol above the recommended dosages. The patient died due to raised intracranial pressure. Cerebral damage was caused by encephalitis due to calcium oxalate crystals. Oxalosis induced by sugar surrogates may be explained either by dose-dependent toxic effects or genetically fixed intolerance.

[Quality control studies of 3 deep-frozen coagulation-active fresh frozen plasma preparations from various suppliers and a new virus-inactivated lyophilized pooled plasma preparation]. / Qualitätskontrollstudien an 3 tiefgefrorenen gerinnungsaktiven Frischplasmapräparaten verschiedener Hersteller und einem virusinaktivierten lyophilisierten Poolplasmapräparat.

Fresh frozen plasma is the most important therapeutic agent in acquired coagulation disorders. We investigated the quality of three conventional fresh-frozen plasma preparations (groups I, II, IV) and one new virus-inactivated lyophilised pooled plasma preparation (group III). In the new plasma preparation we found a significant reduction in coagulation activity, a significantly higher pH value and a highly significant rise in plasma heparin levels. No significant difference in electrolytes, protein levels and concentration or complement activity was found in any of the groups. In conclusion, unlike conventional fresh-frozen plasma, this new virus-inactivated lyophilised pooled plasma preparation does not seem to be suitable for use in therapy of coagulation disorders.

[Important laboratory parameters of deep frozen coagulation active fresh plasma and virus inactivated lyophilized pool plasma]. / Wichtige Laborparameter bei tiefgefrorenen gerinnungsaktiven Frischplasmen und virusinaktivierten lyophilisierten Poolplasmen.

Fresh Frozen Plasma is the most important therapeutic agent in acquired coagulation disorders. We investigated the quality of a new virus-inactivated lyophilisated human pool-plasma (VFL) and conventional fresh frozen plasma (FFP). In VFL we found a significantly reduced coagulation activity, a significantly higher pH-value, a highly significant rise of heparin values and a significantly lower number of thrombocytes. Electrolytes, protein levels and complement activity showed no significant difference. In conclusion, this virus-inactivated lyophilisated human pool plasma does not seem to be susceptible to therapy coagulation disorders like the conventional fresh frozen plasma.

[Post-aggression metabolism and peridural anesthesia: modification of catabolism by anesthesia procedures?]. / Postaggressionsstoffwechsel und Periduralanästhesie: Kataboliebeeinflussung durch Narkoseverfahren?

Postoperative catabolic state of metabolism represents a danger for patients in regard to protein degradation. As postoperative nutrition seems already quite optimal, we examined if anaesthesia, predominantly peridural anaesthesia, would be able to reduce postaggressive metabolism. 20 patients with gastrectomy or subtotal gastric resection were randomized either for a combined anaesthesia with PDA and intubation or for balanced fentanyl analgesia. In both groups the typical characteristics of postaggressive metabolism could be demonstrated without any difference.

[Cerebral convulsion following peridural anesthesia with bupivacaine in cesarean section]. / Zerebraler Krampfanfall nach Periduralanästhesie mit Bupivacain zur Sectio caesarea.

Maternal convulsions and severe fetal bradycardia resulted from the accidental intravascular injection of 0.5% bupivacaine for epidural anesthesia in preparation for caesarean section. Ventilation with oxygen, application of anticonvulsive drugs, relaxation and intubation was promptly performed followed by immediate caesarean section. The newborn was depressed at birth, recovered quickly and showed no neurologic deficits neither in the immediate postnatal period nor in neurobehaviour tests at the age of three months.