Sepsis syndrome and death in trauma patients are associated with variation in the gene encoding tumor necrosis factor.

OBJECTIVE: Patients encountering severe trauma are at risk of developing sepsis syndrome and subsequent multiple organ failure. This is often associated with fatal outcome despite survival of the initial injury. We postulate that variation of the gene coding for tumor necrosis factor (TNF)-alpha is associated with increased occurrence of sepsis syndrome and mortality in trauma patients. DESIGN: Prospective cohort study; validation in an external replication sample. SETTING: Tertiary academic medical center. PATIENTS: We included 159 severely traumatized patients from a single center. Serial blood samples were analyzed for serum concentrations of TNF-alpha and lymphotoxin-alpha (LTA). We genotyped nine polymorphisms in the TNF gene and tested for an association with sepsis syndrome and outcome. Genetic associations were validated in an external replication sample (n = 76). We examined the peripheral blood transcriptome in 28 patients by whole genome-based profiling and validated the results. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Carriage of the TNF rs1800629 A allele was associated with higher TNF-alpha serum concentrations on the first day after trauma and during follow-up (two-sided p = 5.0 x 10(-5)), with development of sepsis syndrome (odds ratio 7.14, two-sided p = 1.2 x 10(-6); external validation sample [n = 76]: odds ratio 3.3, one-sided p = .03), and with fatal outcome (odds ratio 7.65, two-sided p = 1.9 x 10(-6)). Carriage of the TNF rs1800629 A allele was associated with differential expression of genes representing stronger proinflammatory and apoptotic responses compared with carriage of the wild-type allele. CONCLUSIONS: Common TNF gene variants are associated with sepsis syndrome and death after severe injury. These findings are strongly supported by functional data and may be important for developing preemptive anti-inflammatory interventions in carriers of the risk-associated allele.

Response to delivery stress is not mediated by beta-endorphin (1-31).

OBJECTIVE: The aim of the study was to determine the reaction of the melanotroph and corticotroph-type pituitary proopiomelanocortin (POMC) response to vaginal delivery and caesarean section stress. Furthermore, the relationship between the release of pituitary POMC fragments, gonadotropins and sexual steroids were examined. STUDY DESIGN: Blood samples were obtained from 10 women in labour on arrival in the birth room (t(A)), at cervix dilatation of 5 cm (t(B)) and immediately after spontaneous delivery (t(C)) and in 16 patients undergoing elective caesarean section before induction of anaesthesia (t(B)) and immediately after delivery (t(C)). Samples were analysed for cortisol, ACTH, authentic beta-endorphin, beta-endorphin immunoreactive material (IRM), acetyl-N-beta-endorphin IRM (NAC), beta-lipotropin (beta-LPH) IRM, oestradiol (E(2)), progesterone (P), prolactin (PRL), FSH and LH. RESULTS: NAC representing the melanotroph-type pituitary POMC system did not increase during the course of caesarean section or spontaneous labour. In contrast, a significant increase of beta-endorphin IRM, beta-LPH IRM and ACTH were observed, representing an activation of the corticotroph-type POMC system. Highly significant correlations between POMC fragment concentrations during caesarean section and spontaneous labour were also observed. Sexual steroids (E(2) and P) decreased significantly. Except for beta-endorphin IRM and E(2) in course of spontaneous delivery no significant correlation was observed between POMC fragment and gonadotropins or sexual steroids. CONCLUSION: Caesarean section and spontaneous delivery activated the corticotroph but not the melanotroph POMC system.

Increased seroprevalence of parvovirus B 19 IgG in complex regional pain syndrome is not associated with antiendothelial autoimmunity.

The etiology of complex regional pain syndrome (CRPS) is unclear yet. Recently autoantibodies and antecedent viral infections have been discussed to be involved in the pathogenesis of CRPS. We investigated sera from 39 CRPS patients and healthy controls for parvovirus B19 IgG and the occurrence of antiendothelial autoantibodies (AECA). CRPS patients showed a higher seroprevalence of parvovirus B19 IgG than controls (p < 0.01). All CRPS 2 patients were positive. 10.2% of the CRPS patients and 10.0% of the controls had AECA (n.s.) and AECA were not associated with parvovirus B19 seropositivity. Our findings suggest the involvement of parvovirus B19, but not autoantibody-mediated endothelial cell damage, in the pathogenesis of CRPS.

Moderate hypoxia influences excitability and blocks dendrotoxin sensitive K+ currents in rat primary sensory neurones.

Hypoxia alters neuronal function and can lead to neuronal injury or death especially in the central nervous system. But little is known about the effects of hypoxia in neurones of the peripheral nervous system (PNS), which survive longer hypoxic periods. Additionally, people have experienced unpleasant sensations during ischemia which are dedicated to changes in conduction properties or changes in excitability in the PNS. However, the underlying ionic conductances in dorsal root ganglion (DRG) neurones have not been investigated in detail. Therefore we investigated the influence of moderate hypoxia (27.0 +/- 1.5 mmHg) on action potentials, excitability and ionic conductances of small neurones in a slice preparation of DRGs of young rats. The neurones responded within a few minutes non-uniformly to moderate hypoxia: changes of excitability could be assigned to decreased outward currents in most of the neurones (77%) whereas a smaller group (23%) displayed increased outward currents in Ringer solution. We were able to attribute most of the reduction in outward-current to a voltage-gated K+ current which activated at potentials positive to -50 mV and was sensitive to 50 nM alpha-dendrotoxin (DTX). Other toxins that inhibit subtypes of voltage gated K+ channels, such as margatoxin (MgTX), dendrotoxin-K (DTX-K), r-tityustoxin Kalpha (TsTX-K) and r-agitoxin (AgTX-2) failed to prevent the hypoxia induced reduction. Therefore we could not assign the hypoxia sensitive K+ current to one homomeric KV channel type in sensory neurones. Functionally this K+ current blockade might underlie the increased action potential (AP) duration in these neurones. Altogether these results, might explain the functional impairment of peripheral neurones under moderate hypoxia.

Preoperative concentration of beta-lipotropin immunoreactive material in cerebrospinal fluid: a predictor of postoperative pain?

Levels of beta-endorphin immunoreactive material (IRM) in cerebrospinal fluid (CSF) have been reported to correlate inversely with postoperative morphine requirement. Considering proopiomelanocortin (POMC) derivatives as predictors for sensitivity to postoperative pain, we determined authentic beta-endorphin (beta-endorphin(1-31)), beta-lipotropin IRM, N-acetyl-beta-endorphin IRM and ACTH in CSF of 17 patients undergoing hip or knee arthroplasty, before surgery (t(A)), immediately after termination of propofol infusion and still under spinal anesthesia (t(B)), under postoperative pain (t(C)) and one day after surgery (t(D)); patients rated their severity of pain on a visual analogue scale (VAS) at those four times. In all patients CSF concentrations of N-acetyl-beta-endorphin IRM and beta-lipotropin IRM were found to be increased after terminating the propofol infusion with spinal anesthesia still effective at t(B). Patients did not feel pain at times t(A), t(B) or t(D); however, they reported moderate to considerable pain at t(C). There were no correlations of postoperative pain severity at t(C) with ACTH, beta-endorphin(1-31) or N-acetyl-beta-endorphin IRM concentrations in CSF. In contrast, we observed significant inverse correlations (Spearman's rank correlation coefficients between -0.83 and -0.85, p<0.01) for postoperative pain severity with beta-lipotropin IRM concentrations in CSF at t(C), and, in addition, at t(A), t(B) and t(D); thus, postoperative pain severity appeared to be dependent on a central system controlling sensitivity to pain, linked to a POMC system releasing beta-lipotropin IRM into CSF and already active at times t(A) and t(B). We conclude that beta-lipotropin IRM in CSF might be considered to serve as a predictor of sensitivity to postoperative pain.

Plasma levels of corticotroph-type pro-opiomelanocortin derivatives such as beta-lipotropin, beta-endorphin(1-31), or adrenocorticotropic hormone are correlated with severity of postoperative pain.

BACKGROUND: In the pituitary of lower species, pro-opiomelanocortin is expressed in corticotroph cells of the anterior and in melanotroph cells of the neurointermediate lobe; enzymatic processing in the corticotrophs results in the release of adrenocorticotropic hormone, beta-lipotropin, or beta-endorphin. In the melanotrophs, these fragments are further modified, eg, by N-terminal acetylation. In the human pituitary, these enzyme systems are located within the same cells in the anterior lobe. We studied the reactions of the pro-opiomelanocortin system under preoperative conditions as well as under postoperative pain. METHODS: In 17 patients undergoing hip or knee arthroplasty, we determined plasma concentrations of N-acetyl-beta-endorphin immunoreactive material, authentic beta-endorphin [beta-endorphin(1-31)], adrenocorticotropic hormone, beta-lipotropin immunoreactive material, and cortisol, as well as pain severity rated by the patients using a visual analogue scale before surgery, after surgery but still under spinal anesthesia, under postoperative pain, and 1 day after surgery. RESULTS: Only low levels of N-acetyl-beta-endorphin immunoreactive material were measured in 16 out of 17 patients. High concentrations (1st quartile/median/3rd quartile; pmol/L) of adrenocorticotropic hormone (22.5/55.8/124) and beta-lipotropin immunoreactive material (6.6/34.6/142) were observed under postoperative pain, accompanied by a small increase of beta-endorphin(1-31) concentrations (0.0/6.1/10.9). Preoperatively small but significantly elevated levels of corticotroph-type and melanotroph-type pro-opiomelanocortin derivatives were observed; in contrast, spinal anesthesia suppressed all pro-opiomelanocortin fragment release. Postoperative pain severity correlated with postoperative adrenocorticotropic hormone, beta-lipotropin immunoreactive material, and beta-endorphin(1-31) concentrations. CONCLUSIONS: We conclude that the melanotroph-type pro-opiomelanocortin system is not activated under postoperative pain; the increase of corticotroph-type pro-opiomelanocortin fragment levels is different in quantity and proportion under preoperative conditions or postoperative pain, respectively.

Integration of a handheld based anaesthesia rounding system into an anaesthesia information management system.

BACKGROUND: At the University Hospital Giessen, an anesthesia information management system (AIMS) is used for online record keeping of perioperative patient care, but preoperative anaesthesia assessments were still being recorded on paper and subsequently entered into the AIMS. Personal digital assistants (PDAs) seem to be useful instruments to establish a seamless digital anesthesiological documentation. OBJECTIVES: We decided to implement a solution for direct integration of data gathered during the preoperative assessment into the existing data management infrastructure. Parallel to the development of the system, we surveyed the future users to match their wishes and needs as far as possible. SYSTEM DESCRIPTION: A C program embedding the preoperative AIMS' data fields was developed. Data alignment with the Hospital information system (HIS) is controlled by a Java desktop software. The anaesthesiologist completes the available fields at the patient's bedside following the same algorithm and integrity check as the PC version. STATUS REPORT: Overall, 68% of the surveyed physicians supported the implementation of the system. The PDA solution has been available since May 2002. Data replication into the handheld and integration of mobile collected data into the AIMS generally work without problems. The HIS interconnection software converts the PDA file into the AIMS format for further processing. DISCUSSION: The preoperative anaesthetic assessment is a standardised task well suitable for conversion to an electronic data storage medium. Changing from redundant data entry in the OR to direct electronic recording at the patient's bedside seems simply logical. Handheld computers are inexpensive, flexible gadgets to realize this.

Performance and customization of 4 prognostic models for postoperative onset of nausea and vomiting in ear, nose, and throat surgery.

OBJECTIVE: To evaluate the performance of 4 published prognostic models for postoperative onset of nausea and vomiting (PONV) by means of discrimination and calibration and the possible impact of customization on these models. DESIGN: Prospective, observational study. SETTING: Tertiary care university hospital. PATIENTS: 748 adult patients (>18 years old) enrolled in this study. Severe obesity (weight > 150 kg or body mass index > 40 kg/m) was an exclusion criterion. INTERVENTIONS: All perioperative data were recorded with an anesthesia information management system. A standardized patient interview was performed on the postoperative morning and afternoon. MEASUREMENTS: Individual PONV risk was calculated using 4 original regression equations by Koivuranta et al, Apfel et al, Sinclair et al, and Junger et al Discrimination was assessed using receiver operating characteristic (ROC) curves. Calibration was tested using Hosmer-Lemeshow goodness-of-fit statistics. New predictive equations for the 4 models were derived by means of logistic regression (customization). The prognostic performance of the customized models was validated using the "leaving-one-out" technique. MAIN RESULTS: Postoperative onset of nausea and vomiting was observed in 11.2% of the specialized patient population. Discrimination could be demonstrated as shown by areas under the receiver operating characteristic curve of 0.62 for the Koivuranta et al model, 0.63 for the Apfel et al model, 0.70 for the Sinclair et al model, and 0.70 for the Junger et al model. Calibration was poor for all 4 original models, indicated by a P value lower than 0.01 in the C and H statistics. Customization improved the accuracy of the prediction for all 4 models. However, the simplified risk scores of the Koivuranta et al model and the Apfel et al model did not show the same efficiency as those of the Sinclair et al model and the Junger et al model. This is possibly a result of having relatively few patients at high risk for PONV in combination with an information loss caused by too few dichotomous variables in the simplified scores. CONCLUSIONS: The original models were not well validated in our study. An antiemetic therapy based on the results of these scores seems therefore unsatisfactory. Customization improved the accuracy of the prediction in our specialized patient population, more so for the Sinclair et al model and the Junger et al model than for the Koivuranta et al model and the Apfel et al model.

Ketamine impairs excitability in superficial dorsal horn neurones by blocking sodium and voltage-gated potassium currents.

Ketamine shows, besides its general anaesthetic effect, a potent analgesic effect after spinal administration. We investigated the local anaesthetic-like action of ketamine and its enantiomers in Na+ and K+ channels and their functional consequences in dorsal horn neurones of laminae I-III, which are important neuronal structures for pain transmission receiving most of their primary sensory input from Adelta and C fibres. Combining the patch-clamp recordings in slice preparation with the 'entire soma isolation' method, we studied action of ketamine on Na+ and voltage-activated K+ currents. The changes in repetitive firing behaviour of tonically firing neurones were investigated in current-clamp mode after application of ketamine. Concentration-effect curves for the Na+ peak current revealed for tonic block half-maximal inhibiting concentrations (IC50) of 128 microM and 269 microM for S(+) and R(-)-ketamine, respectively, showing a weak stereoselectivity. The block of Na+ current was use-dependent. The voltage-dependent K+ current (K(DR)) was also sensitive to ketamine with IC50 values of 266 microM and 196 microM for S(+) and R(-)-ketamine, respectively. Rapidly inactivating K+ currents (K(A)) were less sensitive to ketamine. The block of K(DR) channels led to an increase in action potential duration and, as a consequence, to lowering of the discharge frequency in the neurones. We conclude that ketamine blocks Na+ and K(DR) channels in superficial dorsal horn neurones of the lumbar spinal cord at clinically relevant concentrations for local, intrathecal application. Ketamine reduces the excitability of the neurones, which may play an important role in the complex mechanism of its action during spinal anaesthesia.

Computers in anesthesia and intensive care: lack of evidence that the central unit serves as reservoir of pathogens.

OBJECTIVE: Computers are becoming increasingly visible in operating rooms (OR) and intensive care units (ICU) for use in bedside documentation. Recently, they have been suspected as possibly acting as reservoirs for microorganisms and vehicles for the transfer of pathogens to patients, causing nosocomial infections. The purpose of this study was to examine the microbiological (bacteriological and mycological) contamination of the central unit of computers used in an OR, a surgical and a pediatric ICU of a tertiary teaching hospital. METHODS: Sterile swab samples were taken from five sites in each of 13 computers stationed at the two ICUs and 12 computers at the OR. Sample sites within the chassis housing of the computer processing unit (CPU) included the CPU fan, ventilator, and metal casing. External sites were the ventilator and the bottom of the computer tower. Quantitative and qualitative microbiological analyses were performed according to commonly used methods. RESULTS: One hundred and ninety sites were cultured for bacteria and fungi. Analyses of swabs taken at five equivalent sites inside and outside the computer chassis did not find any significant-number of potentially pathogenic bacteria or fungi. This can probably be attributed to either the absence or the low number of pathogens detected on the surfaces. CONCLUSION: Microbial contamination in the CPU of OR and ICU computers is too low for designating them as a reservoir for microorganisms.

Local anaesthetics block hyperpolarization-activated inward current in rat small dorsal root ganglion neurones.

(1) Hyperpolarizing voltage steps evoke slowly activating inward currents in a variety of neurones and in cardiac cells. This hyperpolarization-activated inward current (I(h)) is thought to play a significant role in cell excitability, firing frequency, or in setting of the resting membrane potential in these cells. We studied the effects of lidocaine, mepivacaine, QX-314 and bupivacaine as well as its enantiomers on I(h) in the membrane of dorsal root ganglion neurones (DRG). (2) The patch-clamp technique was applied to small dorsal root ganglion neurones identified in 200 micro M thin slices of young rat DRGs. Under voltage-clamp conditions, the whole-cell I(h) current was recorded in the presence of different concentrations of the local anaesthetics. In current-clamp mode the resting membrane potential and the voltage response of DRG neurones to injected current pulses were investigated. (3) I(h) was reversibly blocked by bupivacaine, lidocaine and mepivacaine applied externally in clinically relevant concentrations. Concentration-response curves gave half-maximum inhibiting concentrations of 55, 99 and 190 micro M, respectively. Bupivacaine block of the I(h) current was not stereoselective. No significant effect was observed when QX-314 was applied to the external surface of the membrane. (4) In current-clamp experiments 60 micro M bupivacaine slightly hyperpolarized the membrane. The membrane stimulation by low-amplitude current pulses in the presence of bupivacaine showed an increase of the hyperpolarizing responses. (5) Our findings suggest an important role of the I(h)-block by local anaesthetics in the complex mechanism of drug action during epidural and spinal anaesthesia.

Enhancement of delayed-rectifier potassium conductance by low concentrations of local anaesthetics in spinal sensory neurones.

Combining the patch-clamp recordings in slice preparation with the 'entire soma isolation' method we studied action of several local anaesthetics on delayed-rectifier K(+) currents in spinal dorsal horn neurones. Bupivacaine, lidocaine and mepivacaine at low concentrations (1 - 100 microM) enhanced delayed-rectifier K(+) current in intact neurones within the spinal cord slice, while exhibiting a partial blocking effect at higher concentrations (>100 microM). In isolated somata 0.1 - 10 microM bupivacaine enhanced delayed-rectifier K(+) current by shifting its steady-state activation characteristic and the voltage-dependence of the activation time constant to more negative potentials by 10 - 20 mV. Detailed analysis has revealed that bupivacaine also increased the maximum delayed-rectifier K(+) conductance by changing the open probability, rather than the unitary conductance, of the channel. It is concluded that local anaesthetics show a dual effect on delayed-rectifier K(+) currents by potentiating them at low concentrations and partially suppressing at high concentrations. The phenomenon observed demonstrated the complex action of local anaesthetics during spinal and epidural anaesthesia, which is not restricted to a suppression of Na(+) conductance only.

Increased body mass index and peri-operative risk in patients undergoing non-cardiac surgery.

BACKGROUND: Increased BMI is a well known risk factor for morbidity and mortality in hospitalized nonsurgical patients. However, the published evidence for a comparable effect in surgical patients is scarce. METHODS: This retrospective study was designed to assess the attributable effects of increased BMI (>30 kg/m2) on outcome (hospital mortality, admission to the intensive care unit (ICU), and incidence of intraoperative cardiovascular events (CVE)) in patients undergoing non-cardiac surgery by a computerized anesthesia record-keeping system. The study is based on data-sets of 28065 patients. Cases were defined as patients with BMI >30; controls (BMI 20-25) were automatically selected according to matching variables (ASA physical status, high risk and urgency of surgery, age and sex) in a stepwise fashion. Differences in outcome measures were assessed using univariate analysis. Stepwise regression models were developed to predict the impact of increased BMI on the different outcome measures. RESULTS: 4726 patients (16.8%) were found with BMI >30. Matching was successful for 41.5% of the cases, leading to 1962 cases and controls. The crude mortality rates were 1.1% (cases) vs 1.2% (controls); P =0.50, power=0.88). Admission to ICU was deemed necessary in 6.8% (cases) vs 7.5% (controls), P =0.42, power=0.65, and CVE were detected from the database in 22.3% (cases) vs 21.6% (controls), P =0.30, power=0.60. Using logistic regression analyses, no significant association between higher BMI and outcome measures could be verified. CONCLUSION: Increased BMI alone was not a factor leading to an increased perioperative risk in non-cardiac surgery. This fact may be due to an elevated level of attention while caring for obese patients.

Excessive alcohol consumption and perioperative outcome.

BACKGROUND: Excessive alcohol consumption is a well-recognized factor contributing to premature morbidity and mortality. METHODS: This retrospective, matched cohort study was designed to assess the attributable effects of excessive alcohol consumption on outcome in patients undergoing noncardiac surgery. All data of 28,065 patients operated at a tertiary care university hospital were recorded with a computerized anesthesia record-keeping system. Cases were defined as patients with history of excessive alcohol consumption (>30 g alcohol per day). Controls were selected according to matching variables in a stepwise fashion. RESULTS: In our data set, 928 patients (3.3%) were found with a history of excessive alcohol consumption. Matching was successful in 897 patients (97%). The crude mortality rates for the cases were 1.3% and 1.6%, for the matched controls (P=.084, power=0.85). Prolonged length of hospital stay was observed in 38% versus 33% (P=.013, power=0.50), admission to the intensive care unit was deemed necessary in 11% versus 9% (P=.027, power=0.55), and intraoperative cardiovascular events were detected from the database in 22% versus 21% (P=.053, power=0.61). CONCLUSIONS: In this study, history of excessive alcohol consumption alone is not a factor leading to an increased perioperative risk in noncardiac surgery.

Automatic calculation of the nine equivalents of nursing manpower use score (NEMS) using a patient data management system.

OBJECTIVE: The most recent approach to estimate nursing resources consumption has led to the generation of the Nine Equivalents of Nursing Manpower use Score (NEMS). The objective of this prospective study was to establish a completely automatically generated calculation of the NEMS using a patient data management system (PDMS) database and to validate this approach by comparing the results with those of the conventional manual method. DESIGN: Prospective study. SETTING: Operative intensive care unit of a university hospital. PATIENTS: Patients admitted to the ICU between 24 July 2002 and 22 August 2002. Patients under the age of 16 years, and patients undergoing cardiovascular surgery or with burn injuries were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The NEMS of all patients was calculated automatically with a PDMS and manually by a physician in parallel. The results of the two methods were compared using the Bland and Altman approach, the interclass correlation coefficient (ICC), and the kappa-statistic. On 20 consecutive working days, the NEMS was calculated in 204 cases. The Bland Altman analysis did not show significant differences in NEMS scoring between the two methods. The ICC (95% confidence intervals) 0.87 (0.84-0.90) revealed a high inter-rater agreement between the PDMS and the physician. The kappa-statistic showed good results (kappa>0.55) for all NEMS items apart from the item "supplementary ventilatory care". CONCLUSION: This study demonstrates that automatical calculation of the NEMS is possible with high accuracy by means of a PDMS. This may lead to a decrease in consumption of nursing resources.

Trichloroethanol alters action potentials in a subgroup of primary sensory neurones.

We investigated the effects of 2,2,2-trichloroethanol (TCE), the active metabolite of chloral hydrate, on large-conductance calcium-activated K+ channels (BKCa channels) of dorsal root ganglion (DRG) neurones. In outside-out patches, 2 and 5 mM TCE increased the open probability of BKCa channels to 1.7-fold and 2.8-fold of control, respectively. In 50% of the cells investigated (group A) the action potential (AP) was shortened reversibly by TCE by 20% and the whole-cell outward-current was increased by 44%. Both effects could be antagonized by iberiotoxin. In a second group of neurone (group B), TCE prolonged the AP duration. The effects of TCE in group A, which was 20-fold more potent than ethanol on BKCa channels and AP might contribute to the described analgesic effect of chloral hydrate.

Effects of tourniquet-induced ischemia on the release of proopiomelanocortin derivatives determined in peripheral blood plasma.

Proopiomelanocortin (POMC) is expressed in pituitary, central nervous system, and in a few peripheral tissues. This study addresses the hypothesis that metabolic stressors, such as acidosis, may induce the release of POMC derivatives into the cardiovascular system not only from the pituitary but also from other sites of POMC expression. In our study, we investigated the liberation of POMC derivatives from peripheral tissues under a state of acidosis achieved by tourniquet-induced ischemia, alteration of lactate concentration, and base excess. In eight patients undergoing knee arthroplasty under spinal anesthesia, catheters were inserted into the femoral vein proximally to thigh tourniquet location. Blood was drawn from these catheters 5 min before and 40 s, 5 min, and 10 min after tourniquet deflation to measure plasma concentrations of N-acetyl-beta-endorphin immunoreactive material (IRM), beta-endorphin IRM, authentic beta-endorphin, adrenocorticotropin, lactate, pH, and base excess. In five of eight patients, we found a significant increase of beta-endorphin IRM levels 40 s after tourniquet deflation compared with predeflation levels; 5 and 10 min after tourniquet deflation, the beta-endorphin IRM levels were below the detection limit. Thus beta-endorphin IRM was released from ischemic limb tissues into the cardiovascular system. Only a small part of the determined beta-endorphin IRM corresponded to authentic beta-endorphin. Forty seconds after tourniquet deflation, the beta-endorphin IRM concentration correlated with base excess (r < 0.71; P < 0.05); no significant correlations were found with pH or lactate levels. Thus it was shown here for the first time that ischemic stress may induce the release of beta-endorphin IRM from nonpituitary tissues.

Review of antibiotic drug use in a surgical ICU: management with a patient data management system for additional outcome analysis in patients staying more than 24 hours.

BACKGROUND: A number of developments have been made in computerized patient data management systems (PDMSs), making them of interest to medical and nursing staff as a means of improving patient care. OBJECTIVES: The aim of this study was to assess the capability of a PDMS to record and provide drug-administration data and to investigate whether the PDMS may be used as a means of support for clinical audits and quality control. Furthermore, we assessed whether antibiotic therapy as a surrogate for infections correlates with hospital mortality in patients staying >24 hours in a surgical intensive care unit (SICU). METHODS: Because of its medical and economic importance in ICU treatment, we chose to use the field of antibiotic therapy as an example. A PDMS was used in a 14-bed SICU (Department of Anesthesiology, Intensive Care Medicine, and Pain Therapy, University Hospital Giessen, Giessen, Germany) to record relevant patient data, including therapeutic, diagnostic, and nursing actions. During a 15-month period (April 1, 2000 to June 30, 2001), antibiotic drug therapy was electronically analyzed and presented using the anatomic therapeutic chemical (ATC) category for antibacterials (ATC group, J01) with daily defined doses. Furthermore, the correlation of antibiotic therapy with patient outcome (hospital mortality) was tested using logistic regression analysis. RESULTS: A total of 2053 patients were treated in the SICU. Of these, 58.0% (1190 patients) received antibiotics (4479 treatment days; 13,145 single doses). Cephalosporins (ATC category, J01DA) were used most frequently (1785 treatment days [39.9% of treatment days]), followed by combinations of penicillins with beta-lactam inhibitors (ATC category, J01CR; 1478 treatment days [33.0%]) and imidazole derivatives (ATC category, J01XD; 667 treatment days [14.9%]). The antibiotic therapy lasted <3 days in 65.6% of cases. In 13.8% of cases, the treatment lasted >1 week. A total of 36.7% of cases were treated with only 1 antibiotic agent, 14.1% were given a combination of 2, and 7.2% were given a combination of > or =3 antibiotic agents. Seven hundred twenty-six patients remained in the SICU for >24 hours; 143 (19.7%) died during their hospital stay; 110 (15.2%) in the SICU. The duration of antibiotic therapy (odds ratio [OR], 1.46) and number of different antibiotic drugs used (OR, 2.15) significantly correlated with hospital mortality. CONCLUSIONS: Antibiotic therapy in a SICU can be assessed and analyzed in detail using a PDMS. Furthermore, in this study, the duration of antibiotic therapy and the number of antibiotic agents used correlated with hospital mortality. In further developing PDMSs, it is important for quality-assurance purposes to document the reasons for giving antibiotics and for changing prescriptions. It would also be helpful to integrate certain therapy standards and reminder functions for the duration of therapy in the PDMS.

Quantitative determination of free intracellular alpha-keto acids in neutrophils.

For the first time, a procedure is described for the quantitative analysis of free alpha-keto acid content in human neutrophils (PMNs) relative to single cell number by reversed-phase fluorescence high-performance liquid chromatography. The procedure is minimally invasive and is unsurpassed in the quality of PMN separation, ease of sample preparation as well as sample stability. This method can satisfy the rigorous demands for an ultra-sensitive, comprehensive and rapid intracellular alpha-keto acid analysis in particularly for the surveillance of severe diseases as well as cellular or organ dysfunction.