Impact of shed blood products on stimulated cytokine release in an in vitro model of transfusion.

BACKGROUND: Blood transfusion is reported to suppress the recipient's immune system. To avoid allogenic transfusion, post-operative shed blood retransfusion is a commonly used method. The aim of this study was to investigate the dose-related impact of post-operatively collected shed blood products on the stimulated cytokine release in an in vitro model of transfusion. METHODS: Venous blood samples obtained from 20 patients undergoing hip arthroplasty were mixed with post-operatively collected unprocessed, processed, and irradiated shed blood as well as normal saline as a control. Shed blood was processed by centrifugation and separating the cellular fraction from the soluble fraction and washing the cellular fraction with phosphate buffered saline to eliminate any cell fragments and other substances. Mixing ratios were 1:3, 1:1, and 3:1. Endotoxin-stimulated release of Tumor Necrosis Factor-alpha (TNF-α) was measured after 24 h of culture by enzyme-linked immunosorbent assay. RESULTS: Unprocessed, irradiated shed blood and the soluble fraction caused a significant suppression of stimulated TNF-α release compared to control. The addition of the cellular shed blood fraction had no significant influence on the TNF-α release compared to control. CONCLUSION: Shed blood and its components caused a dose-independent immunomodulation as indicated by a suppressed stimulated TNF-α release. Leukocytes seem to play a minor role, as we observed a sustained suppression after transfusion of γ-irradiated shed blood. Only the elimination of soluble factors by centrifugation and followed by an additional washing step prevented the observed suppression of TNF-α. Thus, we assume that washing of shed blood can prevent potential detrimental effects.

[Necessity for treatment of psychiatric emergencies in the emergency medical service. Evaluation of the "indicator for psychiatric pharmacotherapy"]. / Behandlungsbedürftigkeit psychiatrischer Notfälle im Notarztdienst. Evaluierung des "Indikator für psychiatrische Pharmakotherapie"

BACKGROUND: Psychiatric emergency situations (PES) are common in the physician-based emergency medical system (EMS) in Germany. However, many emergency physicians (EP) feel insecure in assessing the necessity for treatment of these patients. The aim of this investigation was to evaluate whether a short, newly developed questionnaire (Indicator for Psychiatric Pharmacotherapy, IPP) is able to help EPs in deciding for or against pharmacological treatment. PATIENTS AND METHODS: The protocols of the EMS at the Saarland University Hospital were prospectively collected over a 1-year period and PESs were identified and analyzed in detail. The 7-item IPP, which focuses on the most relevant psychiatric symptoms, was to be completed for each PES. RESULTS: Among all calls for an EP (2,114) 250 (11.8%) were classified as a PES. The most frequent diagnoses were alcoholic intoxication, state of agitation and suicide attempts. Of the IPP questionnaires 193 could be evaluated and in 31.2% of all PESs a specific psychiatric medication was administered. These patients scored significantly higher in the IPP compared to those who did not receive medication (8.0 ± 3.9 compared to 5.6 ± 3.2, p < 0.001). The IPP items "anxiety", "agitation/aggression", "mood" and "physical symptoms/disorders" had the highest impact on the administration of psychotherapeutic drugs. DISCUSSION: The IPP can be a valuable tool to assess the necessity of pharmacological treatment for patients in PESs. The assessment of the symptom categories "anxiety", "agitation/aggression", "mood" and "physical symptoms/disorders" seems to be sufficient to estimate a need for treatment.

Droperidol has comparable clinical efficacy against both nausea and vomiting.

BACKGROUND: Droperidol is commonly noted to be more effective at preventing postoperative nausea (PON) than vomiting (POV) and it is assumed to have a short duration of action. This may be relevant for clinical decisions, especially for designing multiple-drug antiemetic regimens. METHODS: We conducted a post hoc analysis of a large multicentre trial. Within this trial, 1734 patients underwent inhalation anaesthesia and were randomly stratified to receive several antiemetic interventions according to a factorial design, one of which was droperidol 1.25 mg vs placebo. We considered differences to be significant when: (i) point estimates of one outcome are not within the limits of the confidence interval (CI) of the other outcome; and (ii) differences in risk ratio (also known as relative risks, RR) are at least 20%. RESULTS: Over 24 h, nausea was reduced from 42.9% in the control to 32.0% in the droperidol group, corresponding to a relative risk (RR) of 0.75 (95% CI from 0.66 to 0.84). Vomiting was reduced from 15.6% to 11.8%, and therefore associated with a similar RR of 0.76 (0.59-0.96). In the early postoperative period (0-2 h), droperidol prevented nausea and vomiting similarly, with an RR of 0.57 (0.46-0.69) for nausea and 0.56 (0.37-0.85) for vomiting. In the late postoperative period (2-24 h), the RR was again similar with 0.83 (0.72-0.96) for nausea compared with 0.89 (0.66-1.18) for vomiting but significantly less compared with the early postoperative period. CONCLUSIONS: We conclude that droperidol prevents PON and POV equally well, yet its duration of action is short-lived.

Impact of platelets and fresh frozen plasma in contrast to red cell concentrate on unstimulated and stimulated cytokine release in an in vitro model of transfusion.

Transfusion of blood may contribute to immunomodulation. Leuco-depleted standard blood products are supposed to result in less immunomodulation compared with whole blood. To determine the influence of leuco-depleted blood products on the cytokine response, red blood cell concentrates (RBC), fresh frozen plasma (FFP) and platelet concentrates (PC) were investigated in an in vitro model of blood transfusion. Leuco-depleted standard blood bank RBC, FFP and PC were mixed in vitro with AB0 compatible venous blood from healthy volunteers in ratios of 3:1, 1:1 and 1:3. Specimens were incubated in presence or absence of lipopolysaccharide, 1 mug/ml. After 24 h of incubation cytokine release of tumour necrosis factor (TNF)-alpha and interleukin-10 (IL-10) was measured in cell culture supernatants by means of enzyme-linked immunsorbent assay. Addition of RBC, FFP and PC to venous blood from healthy volunteers led to a significant and dose-dependent increase in spontaneous TNF-alpha and IL-10 release. After endotoxin stimulation, RBC, FFP and PC significantly suppressed the TNF-alpha response, while the stimulated release of IL-10 tended to increase, reaching significance only after high doses of FFP. Addition of leuco-depleted blood products changed the spontaneous and stimulated cytokine response in an in vitro model of transfusion. These data may suggest a possible contribution of transfused FFP and PC to immunomodulation after transfusion similar to RBC.

[Nausea and vomiting in the postoperative phase. Expert- and evidence-based recommendations for prophylaxis and therapy]. / Ubelkeit und Erbrechen in der postoperativen Phase. Experten- und evidenzbasierte Empfehlungen zu Prophylaxe und Therapie.

There are no consensus guidelines for the management of postoperative nausea and vomiting (PONV) in German speaking countries. This meeting was intended to develop such guidelines on which individual health care facilities can derive their specific standard operating procedures (SOPs). Anesthesiologists reviewed published literature on key topics which were subsequently discussed during two meetings. It was emphasized that recommendations were based on the best available evidence. The clinical relevance of individual risk factors should be viewed with caution since even well proven risk factors, such as the history of PONV, do not allow the identification of patients at risk for PONV with a satisfactory sensitivity or specificity. A more useful approach is the use of simplified risk scores which consider the presence of several risk factors simultaneously. Most individual antiemetic interventions for the prevention of PONV have comparable efficacy with a relative risk reduction of about 30%. This appears to be true for total intravenous anesthesia (TIVA) as well as for dexamethasone and other antiemetics; assuming a sufficiently high, adequate and equipotent dosage which should be weight-adjusted in children. As the relative risk reduction is context independent and similar between the interventions, the absolute risk reduction of prophylactic interventions is mainly dependent on the patient's individual baseline risk. Prophylaxis is thus rarely warranted in patients at low risk, generally needed in patients with a moderate risk and should include a multimodal approach in patients at high risk for PONV. Therapeutic interventions of PONV should be administered promptly using an antiemetic which has not been used before. The group suggests algorithms where prophylactic interventions are mainly dependent on the patient's risk for PONV. These algorithms should provide evidence-based guidelines allowing the development of SOPs/policies which take local circumstances into account.

[Influence of gender on propofol consumption and recovery times]. / Einfluss des Geschlechts auf Propofolverbrauch und Aufwachzeiten bei standardisierter Anästhesietiefe.

INTRODUCTION: We investigated gender differences of drug consumption and recovery times for propofol-remifentanil anaesthesia. METHODS: Adult patients scheduled for minor orthopaedic surgery were randomised to receive a propofol-remifentanil anaesthesia controlled either by EEG monitoring (Narcotrend or BIS) or solely by clinical parameters. Anaesthesia was induced with remifentanil 0.4 microg/kg/min and a propofol target-controlled infusion (TCI) at 3.5 microg/ml. After intubation remifentanil was reduced to 0.2 microg/kg/min whereas propofol TCI was adjusted according to clinical parameters or to the following EEG target values: during maintenance to "D(0)" (Narcotrend) or "50" (BIS), 15 min before the end of surgery to "C(1)" (Narcotrend) or "60" (BIS). Recovery times were recorded and average normalised propofol consumption was calculated from induction and maintenance doses. RESULTS: A total of 60 male and 60 female patients completed the study. Gender differences were observed for recovery times (with standard practice) and for propofol consumption (with BIS monitoring). In the standard protocol group, propofol consumption was nearly identical for male and female patients whereas recovery times were significantly longer in the male group. In both EEG-guided groups propofol consumption was less for male patients while recovery times were slightly longer. In the group of female patients higher propofol TCI concentrations had to be used to reach the same BIS or Narcotrend values. CONCLUSION: With propofol-remifentanil anaesthesia, gender has impact on recovery times and propofol consumption. If the same amounts of propofol are applied, males awake later, with BIS or Narcotrend monitoring males receive less propofol for comparable EEG effects.

[A factorial trial of six interventions for the prevention of postoperative nausea and vomiting]. / Eine faktorielle Studie von 6 Interventionen zur Vermeidung von Ubelkeit und Erbrechen nach Narkosen Ergebnisse des "International Multicenter Protocol to assess the single and combined benefits of antiemetic strategies in a controlled clinical trial of a 2x2x2x2x2x2 factorial design" (IMPACT).

BACKGROUND: Untreated, one third of patients who undergo surgery will have postoperative nausea and vomiting. Although many trials have been conducted, the relative benefits of prophylactic antiemetic interventions given alone or in combination remain unknown. METHODS: In a randomized, controlled trial of factorial design, 5,199 patients at high risk for postoperative nausea and vomiting were randomly assigned to 1 of 64 possible combinations of 6 prophylactic interventions: 1) 4 mg of ondansetron or no ondansetron; 2) 4 mg of dexamethasone or no dexamethasone; 3) 1.25 mg of droperidol or no droperidol; 4) propofol or a volatile anesthetic; 5) nitrogen or nitrous oxide; 6) remifentanil or fentanyl. The primary aim parameter was nausea and vomiting within 24 h after surgery, which was evaluated blindly. RESULTS: Ondansetron, dexamethasone, and droperidol each reduced the risk of postoperative nausea and vomiting by about 26%, propofol reduced the risk by 19%, and nitrogen by 12%. The risk reduction with both of these agents (i.e., total intravenous anesthesia) was thus similar to that observed with each of the antiemetics alone. All the interventions acted independently of each other and independently of the patients' baseline risk. Consequently, the relative risks associated with the combined interventions could be estimated by multiplying the relative risks associated with each intervention. However, absolute risk reduction was a critical function of patients' baseline risk. CONCLUSIONS: Because antiemetic interventions are similarly effective and act independently, the safest or least expensive should be used first. Prophylaxis is rarely warranted in low-risk patients, moderate-risk patients may benefit from a single intervention, and multiple interventions should be reserved for high-risk patients.

[Haemodynamic effects following preoperative hypervolemic haemodilution with hypertonic hyperoncotic colloid solutions in coronary artery bypass graft surgery]. / Hämodynamische Reaktionen nach präoperativer hypervolämischer Hämodilution mit hyperton-hyperonkotischen Kolloiden bei Koronarbypassoperationen.

OBJECTIVE: Using hyperoncotic colloids as volume replacement to provide haemodynamic stability appears to be a suitable approach to diminish fluid overload and subsequent interstitial edema during cardiac surgery. The aim of the present study was to investigate for the first time the haemodynamic effects following preoperative haemodilution with different hypertonic hyperoncotic colloid solutions in patients undergoing coronary artery bypass grafting. METHODS: A total of 43 patients with normal left ventricular ejection fraction, undergoing elective coronary artery bypass grafting received preoperatively after induction of anaesthesia according to randomisation the following solutions: 1: 750 ml/m(2) (body surface area) NaCl 0.9% ( n=10, control group, NACL), 2: 250 ml/m(2) 10% HES 200/0.5 plus 400 ml/m(2) NaCl 0.9% ( n=9, HES), 3: 250 ml/m(2) 10% dextran 40 plus 300 ml/m(2) NaCl 0.9% ( n=8, DEX), 4: 150 ml/m(2) hypertonic NaCl (7.2%) 10% HES 200/0.5 (n=8, HYPER-HES), 5: 150 ml/m(2) hypertonic NaCl (7.2%) 10% dextran 60 ( n=8, HYPER-DEX). Haemodynamic measurements were performed immediately before and 15 min after haemodilution and up to 60 min after termination of extracorporeal circulation in 10 min intervals. Fluid balances were calculated separately, during the time period of surgery, postoperatively up to 24 h after termination of surgery, and during the course of extracorporeal circulation. RESULTS: After haemodilution with colloid solutions, a marked increase was observed in all patients and with HYPER-HES and HYPER-DEX a statistically significant increase in cardiac index (CI: +38%, +54%), stroke volume index (SVI: +42%, +40%), and oxygen availability (DO2: +34%; +41%), respectively, was observed during the pre-bypass period. At the same time right and left ventricular filling pressures increased slightly in all patients but these changes did not differ among the treatment groups. Heart rate and mean arterial pressure remained almost unchanged in all groups. The amount of crystalloid solutions required by the patients during surgery was markedly decreased with HES and DEX and significantly decreased with HYPER-HES and HYPER-DEX (1,013+/-341 ml/m(2), 1,096+/-234 ml/m(2)) compared to the control group NACL (1629+/-426 ml/m(2)). Serum sodium concentrations increased with HYPER-HES and HYPER-DEX to maximal values of 150+/-3 mmol/l and 149+/-4 mmol/l, respectively (baseline 141+/-3 mmol/l, 141+/-1 mmol/l) CONCLUSIONS: Compared to isotonic saline solution, preoperative volume replacement with hyperoncotic colloids improves haemodynamic conditions during the pre-bypass period in patients with normal left ventricular function undergoing coronary artery bypass grafting. Additionally intraoperative crystalloid solution requirements are reduced. The volume saving effects are increased with administration of hyperoncotic colloids in a preparation with hypertonic saline solution, whereas the choice of the colloid, either hydroxyethyl starch or dextran seems to be of minor importance.

[Procalcitonin plasma concentrations and systemic inflammatory response following different types of surgery]. / Procalcitoninplasmakonzentration und systemische inflammatorische Antwort nach verschiedenen operativen Eingriffen.

OBJECTIVE: Procalcitonin (PCT) is currently recommended as a suitable parameter to detect and to evaluate the course of bacterial, fungal or parasitic infections. However, recent studies provide evidence that surgical trauma and humoral mediators of inflammation, respectively,may induce PCT synthesis, thereby reducing the validity and reliability of PCT as an "infection-monitoring" parameter. The aim of the present study was to assess and to compare PCT and CRP (C-reactive protein) plasma concentrations in patients presenting without infection following different types of surgery in the absence or presence of a systemic inflammatory response syndrome (SIRS). METHODS: PCT and CRP plasma concentrations were assessed daily on postoperative days 1-5 and maximal values were determined in 94 patients. The patients were allocated to four groups of different types of surgery as follows: A: minor, primarily aseptic surgery, B: major abdominal surgery, C: major vascular surgery and D: thoracic surgery including esophagectomy. All categories were divided into two subgroups representing patients with and without SIRS, respectively. RESULTS. PCT plasma concentrations increased moderately compared to normal values in 21% of patients after minor and aseptic surgery (A), in 27% and 41% after major vascular (C) and thoracic (D) surgery, respectively, and in 65% of patients after major abdominal (B) surgery. The difference between PCT concentrations in patients undergoing major abdominal surgery and the patients after minor, aseptic surgery was significant ( p<0,05: A vs. B). Comparing the patients presenting with or without systemic inflammatory response (SIRS), no significant differences in PCT concentrations between groups could be observed. In the majority of patients PCT values rose to peak levels on the first and second postoperative days, followed by a rapid decline based on the plasma half-life of PCT. In contrast, postoperative CRP plasma concentrations were markedly elevated above normal values in all investigated patients during the whole observation period. Between-categories statistical analysis revealed significant differences comparing patients undergoing minor and aseptic surgery with patients after major vascular, and thoracic surgery, respectively ( p<0,05,A vs.C, D). CRP concentrations were significantly increased in patients with systemic inflammatory response compared to patients with normal postoperative course in surgical categories B, C, and D, respectively ( p<0,05). CONCLUSIONS: Postoperative PCT plasma concentrations in patients presenting without signs of infection are largely influenced by the type of surgical procedure. During the first and second postoperative day PCT concentrations are more frequently elevated in patients after major abdominal, major vascular and thoracic surgery compared to patients undergoing minor, aseptic operations. Thus an "infection monitoring" considering PCT value analysis during the postoperative course may transiently be impeded after major and particularly after intestinal surgery during the first 2 days postoperatively, whereas it appears not to be substantially affected by the presence or absence of systemic inflammatory response.

[Narcotrend stages and end-tidal desflurane concentrations. An investigation during recovery from desflurane/remifentanil anaesthesia]. / Narcotrend-Stadien und endexspiratorische Desflurankonzentrationen Eine Untersuchung bei Ausleitung von Desfluran-Remifentanil-Anästhesien.

OBJECTIVE: [corrected] As indicated by the manufacturer the EEG monitor Narcotrend trade mark (MonitorTechnik, Bad Bramstedt) can be used to analyse EEG effects of volatile anaesthetics, however, published data are missing. This study evaluated the emergence from a desflurane/remifentanil anaesthetic and was designed to investigate the relationship between Narcotrend stages (version 2.0 AF) and end-tidal desflurane concentrations and to identify the pattern of changes of the Narcotrend stages during recovery. METHODS: Adult patients scheduled for orthopaedic surgery were premedicated with 0.15 mg/kg diazepam orally in the evening and on the morning before surgery. Narcotrend EEG electrodes were positioned on the patient's forehead as recommended by the manufacturer. For induction of anaesthesia, remifentanil was infused at 0.4 microgram/kg/min and propofol 2 mg/kg was given for hypnosis. After neuromuscular blockade and orotracheal intubation, remifentanil was reduced to 0.2 microgram/kg/min, and desflurane in O(2)/air was added according to clinical needs. After termination of surgery, administration of anaesthetics was discontinued and simultaneously, the fresh gas flow was increased to 10 l/min of O(2) while the respirator pattern was left unchanged. Narcotrend stages and end-tidal desflurane concentrations were recorded as data pairs at intervals of 1 min during emergence from anaesthesia; data evaluation included the last 7 min before extubation. RESULTS: A total of 50 patients (mean age +/-SD 44.4+/-13.0 years) were studied and 400 data pairs were obtained. A decreasing depth of anaesthesia as indicated by the Narcotrend was associated with significantly lower end-tidal desflurane concentrations: for E (general anaesthesia with deep hypnosis) 3.6+/-1.0 vol%, for D (general anaesthesia) 1.7+/-0.8 vol%, for C (light anaesthesia) 0.7+/-0.3 vol% and for A and B (awake or sedated) 0.5 vol%. A reduction of end-tidal desflurane concentrations was accompanied by a shift of Narcotrend stages from C/D/E to A/B/C. CONCLUSION: During emergence from desflurane/remifentanil anaesthesia, a reduction of end-tidal desflurane concentrations was detected by the EEG monitor Narcotrend and classified as a typical change of distribution of Narcotrend stages.

Comparison of the effects of remifentanil or fentanyl on anaesthetic induction characteristics of propofol, thiopental or etomidate.

BACKGROUND AND OBJECTIVE: This prospective, randomized, double-blinded study was designed to compare the effects of remifentanil or fentanyl on anaesthetic induction characteristics of propofol, thiopental or etomidate. METHODS: Seventy-two patients were enrolled in six groups of 12 individuals each. In three groups, fentanyl was given as a bolus dose of 1.5 microg kg(-1), whereas the others received a remifentanil infusion at 0.5 microg kg(-1) min(-1). Five minutes later, propofol, thiopental or etomidate were titrated to a state of unresponsiveness. Assessment included the amounts of drug necessary for induction, haemodynamics and the times to apnoea, loss of eyelash reflex, and the release of a water-filled syringe held in the patient's hand. RESULTS: Induction times to loss of the eyelash reflex were significantly shorter in the remifentanil than in the fentanyl groups: with propofol 50.7 +/- 13.6s (mean +/- SD) versus 74.9 +/- 27.0s (P < 0.01), with thiopental 42.9 +/- 16.8s versus 77.2 +/- 27.8s (P < 0.01) and with etomidate 54.7 +/- 17.6s versus 72.3 +/- 24.0s (P < 0.05). The times to respiratory arrest or for the syringe to fall were significantly shorter with remifentanil than with fentanyl for propofol and for thiopental, but not for etomidate. In terms of dosages per kg body weight necessary to achieve unresponsiveness, less propofol (-29%, P < 0.05), thiopental (-25%, P < 0.05) or etomidate (-32%, P < 0.01) was necessary with remifentanil than with fentanyl. Haemodynamic responses to tracheal intubation were controlled more effectively with remifentanil. However, within the remifentanil groups, mean arterial pressure significantly decreased during induction: -26% with propofol, -181% with thiopental and -14% with etomidate (all P < 0.01). CONCLUSIONS: During anaesthetic induction, a remifentanil infusion of 0.5 microg kg(-1) min(-1) over 5 min is a suitable alternative to a 1.5 microg kg(-1) bolus dose of fentanyl: induction times are shorter with reduced amounts of propofol, thiopental or etomidate.

Recovery after remifentanil and sufentanil for analgesia and sedation of mechanically ventilated patients after trauma or major surgery.

We investigated the analgesic effect and the neurological recovery time after administration of remifentanil in mechanically ventilated patients in an intensive care unit. Twenty patients, after trauma or major surgery with no intracranial pathology, were randomized to receive either remifentanil/propofol (n=10) or sufentanil/propofol (n=10). A sedation score and a simplified pain score were used to assess adequate sedation and analgesia. Medication was temporarily stopped after 24 h. Immediately before and 10 and 30 min after, the degree of sedation and pain score were evaluated. Adequate analgesia and sedation was achieved with remifentanil 10.6 microg kg(-1) h(-1) and propofol 2.1 mg kg(-1) h(-1), or sufentanil 0.5 microg kg(-1) h(-1) and propofol 1.3 mg kg(-1) h(-1). The difference in propofol dose between groups was significant. Ten minutes after terminating the medication, the degree of sedation decreased significantly after remifentanil and all patients could follow simple commands. During the following 20 min, all patients with remifentanil emerged from sedation and complained of considerable pain. By contrast, in the sufentanil group, only six (7) responded to commands after 10 (30) min and their pain score remained essentially unchanged during the 30-min observation period. We conclude that, in contrast to sufentanil, remifentanil facilitates rapid emergence from analgesia and sedation, allowing a clinical neurological examination within 10-30 min in mechanically ventilated patients with no intracranial pathology.

[Gamma-hydroxybutyric acid-ethanolamide (LK 544). The suitability of LK 544 for sedation of patients in intensive care in comparison with midazolam]. / Gammahydroxybuttersäure-Ethanolamid (LK 544). Die Eignung von LK 544 zur Sedierung von Intensivpatienten im Vergleich mit Midazolam.

OBJECTIVE: In this phase 2 study gammahydroxybutyric acid-ethanolamide (GHB-ethanolamide) was compared with midazolam for sedation of patients in the intensive care unit (ICU). GHB-ethanolamide is a new derivative of gammahydroxybutyric acid, a drug commonly used for sedation in intensive care patients. METHODS: A total of 29 non-intubated, spontaneously breathing patients following major surgery, were randomly assigned to 2 groups: group A (n = 14) received 150 mg/kg GHB-ethanolamide i.v. followed by 150 mg/kg/h. Group B (n = 15) received 0.025 mg/kg midazolam i.v. followed by 0.025 mg/kg/h. The degree of sedation was assessed over a 3-5 h period both clinically by the Ramsay Score and by the spectral frequency index (SFx), derived by continuous computerized EEG recording (CATEEM). RESULTS: EEG: the SFx showed a significantly deeper sedation compared to baseline values, 10, 60 and 120 min after start of sedation in the GHB-ethanolamide group. By contrast, no difference could be observed compared to baseline values in the midazolam group. A comparison between both groups showed a deeper sedation in the GHB group 60 and 120 min after start of sedation. The Ramsay Score increased from baseline values of 2.0 (2.0/2.0) to 3.0 (2.0/3.0) during sedation (Median (25th/75th percentile) and no significant differences could be observed between groups. In the Midazolam group the sedation of two patients had to be terminated because of side effects (Ramsay Score 6 and paradoxical, agitated reaction). CONCLUSIONS: GHB-ethanolamide produces adequate sedation for extubated and spontaneously breathing ICU patients. The drug might be safer than midazolam with regards to side effects such as respiratory depression.

The Narcotrend--a new EEG monitor designed to measure the depth of anaesthesia. A comparison with bispectral index monitoring during propofol-remifentanil-anaesthesia.

INTRODUCTION: The Narcotrend is a new EEG monitor designed to measure the depth of anaesthesia based on a 6-letter classification from A (awake) to F (general anaesthesia with increasing burst suppression) and divided into 14 substages (A, B0-2, C0-2, D0-2, E0,1, F0,1). This study was designed to investigate the assessment of the depth of anaesthesia as measured by the Narcotrend in comparison with bispectral index monitoring (BIS). METHODS: Both BIS and Narcotrend EEG electrodes were positioned on the patient's forehead as recommended by the manufacturers. All patients were premedicated with diazepam 0.15 mg/kg orally in the evening and on the morning before surgery. Induction of anaesthesia was started with a remifentanil infusion at 0.4 microgram/kg/min; 5 min later propofol was given for hypnosis using a target-controlled infusion initially started at 3.5 micrograms/ml. After loss of consciousness patients received 1.2 mg/kg of suxamethonium. Immediately after intubation, remifentanil was reduced to 0.2 microgram/kg/min, and the depth of anaesthesia was adjusted according to clinical needs by regulating the propofol target-controlled-infusion. BIS values and Narcotrend stages were recorded as data pairs in intervals of 1 min during anaesthetic induction and emergence, and in intervals of 5 min during maintenance of anaesthesia. RESULTS: Fifty patients undergoing orthopaedic surgery were studied and 2031 data pairs were obtained. An increasing depth of anaesthesia as indicated by the Narcotrend was associated with significantly lower mean BIS values. With BIS values between 100 and 85 (representing awake patients), 95.5% of all data pairs indicated a Narcotrend stage A or B. In case the BIS was found to be 65-40 (representing general anaesthesia) the corresponding Narcotrend stages were measured as D (52.4%) or E (41.1%). No patient complained of intraoperative recall when interviewed on the 1st and 3rd postoperative day. CONCLUSIONS: We could demonstrate that an increase of the hypnotic component of anaesthesia as indicated by BIS is accompanied by corresponding effects as displayed by the Narcotrend during propofol-remifentanil anaesthesia. The Narcotrend stages D or E are assumed equivalent to BIS values between 64 and 40 indicating general anaesthesia.

[Less pain on injection by a new formulation of propofol? A comparison with propofol LCT]. / Weniger Injektionsschmerz durch Propofol-MCT/LCT? Ein Vergleich mit Propofol-LCT.

BACKGROUND: Pain on injection is a major disadvantage of propofol, experienced by the vast majority of patients. Since the traditional formulation has almost normal osmolality and pH, it is hypothesised that the concentration of free propofol in the aqueous phase of the emulsion is responsible for the pain and that reducing the amount of free propofol would also reduce the frequency and intensity of pain on injection. This study was designed to investigate whether pain on injection can be reduced in frequency and intensity by a new formulation of propofol. METHODS: We performed a monocentre, controlled, randomised, double-blind study to compare the pain produced by intravenous injection of a new propofol preparation (propofol-MCT/LCT) with standard propofol in patients undergoing elective surgical procedures. A total of 184 non-premedicated patients received either 1% propofol prepared in a mixture of medium and long chain triglycerides (Propofol-MCT/LCT, Propofol- Lipuro, B. Braum Melsungen AG) or standard 1% propofol prepared exclusively in long chain triglycerides (Propofol-LCT; Disoprivan, AstraZeneca) into a vein of the dorsal hand for induction of anaesthesia. Anaesthesia was maintained by TIVA with propofol and remifentanil. Pain on injection was recorded and graded as none, mild, moderate or severe. RESULTS: Patients receiving propofol-MCT/LCT had a significantly lower incidence of pain on injection compared to the standard propofol group (37% vs 64%) with the intensity of pain also being less severe. There were no differences between both groups in propofol dosage for induction (3.2 +/- 0.8 mg/kg vs 3.3 +/- 0.9 mg/kg) and maintenance of anaesthesia (3.4 +/- 0.6 mg/kg/h vs 3.2 +/- 0.5 mg/kg/h), remifentanil dosage (25 +/- 6 micrograms/kg/h vs. 24 +/- 6 micrograms/kg/h), intraoperative hemodynamics, recovery parameters and postoperative patient satisfaction. Postoperative thrombophlebitis at the injection site for propofol was not observed in any of the patients. CONCLUSIONS: Propofol-MCT/LCT produced significantly less pain on injection when compared to standard propofol in ASA I and II patients undergoing elective surgery. Pain was also significantly less severe, with both effects presumably being due to the lower concentration of free propofol in the MCT/LCT-preparation. With regard to injection pain propofol-MCT/LCT offers significant a advantage over standard propofol.