Search PubMed⌕ Search

Biomedical subjects

G Hempelmann

Publications and source records attributed to G Hempelmann.

At least 217 records · Page 12Linked to original sources
PubMed1996

[Possible applications of the "patch-clamp" method in anesthesiologic research; comment].

The patch clamp technique has gained considerable significance during the past two decades since it was developed. Many mechanisms of cell function have been elucidated by the application of the patch clamp method because it was now possible to demonstrate and investigate directly single ion channels in excitable cell membranes. An important discovery, as far as medicine was concerned, was that various clinically used substances interact directly with ion channels. Local anaesthetics, antiarrhythmics, antidiabetics, muscle relaxants are a few examples. For these reasons, more and more clinical physicians use the patch clamp method for their specific investigations. Collaboration between a clinical institute and a basic research department can often be found, which gives clinical research more background and basic science more practical aspects.

Anesthetics↗
PubMed1996

Influence of different volume therapy regimens on regulators of the circulation in the critically ill.

Various vasoactive substances are involved in the regulation of the macro- and microcirculation. We have investigated if these regulators change during long-term volume therapy with human albumin (HA) or hydroxyethylstarch solution (HES) in trauma and sepsis patients. To maintain pulmonary capillary wedge pressure (PCWP) at 10-15 mm Hg, either 20% HA (HA-trauma, n = 14; HA-sepsis, n = 14) or 10% low-molecular weight HES solution (HES-trauma, n = 14; HES-sepsis, n = 14) were infused for 5 days, otherwise patient management did not differ between the two groups (trauma/sepsis). Mean arterial pressure (MAP), heart rate (HR), PCWP and cardiac index (CI) were monitored in all patients. Liver function was assessed using the monoethylglycinexylidide (MEGX) test, and gastric intramucosal pH (pHi) was monitored by tonometry to assess splanchnic perfusion. Plasma concentrations of vasopressin, endothelin-1, adrenaline, noradrenaline, atrial natriuretic peptide and 6-keto-prostaglandin F1 alpha were measured from arterial blood samples. All measurements were carried out on the day of admission to the intensive care unit (trauma patients) or on diagnosis of sepsis, and daily over the next 5 days at 12:00. MAP, HR and PCWP did not differ between the corresponding subgroups (trauma/sepsis). Cl increased significantly more in the HES than in the HA groups. pHi and MEGX plasma concentrations did not differ in the trauma patients throughout the study. Both were lower than normal in the sepsis groups and increased more markedly in the HES than in the albumin-treated patients (P < 0.05). In the trauma patients, concentrations of all vasoactive regulators were very similar in both groups. In both sepsis groups, vasopressors (vasopressin, endothelin-1, noradrenaline and adrenaline) were significantly increased above normal at baseline and decreased more markedly in HES than in HA patients. Concentrations of atrial natriuretic peptide increased only in the HA patients (from 159 (SD 31) to 215 (38) pg ml-1 on day 2). Plasma concentrations of 6-keto-prostaglandin F1 alpha decreased significantly only in the HES sepsis patients (from 112 (25) to 47 (15) pg ml-1).

Adult↗
PubMed1996

The effects of albumin versus hydroxyethyl starch solution on cardiorespiratory and circulatory variables in critically ill patients.

Sufficient intravascular fluid therapy is of major importance in the treatment of the critically ill patient. The present study assessed whether the cardiorespiratory response of long-term volume replacement with low-molecular weight (LMW) hydroxyethyl starch solution (HES) differs from that of human albumin (HA). According to a randomized sequence, 30 trauma patients (injury severity score [ISS] between 15 and 30) and 30 sepsis patients (secondary to major general surgery) received either 10% HES (mean molecular weight 200,000 daltons; HES trauma [n = 15], HES sepsis [n = 15]) or human albumin 20% (HA trauma [n = 15], HA sepsis [n = 15]) over 5 days to keep pulmonary capillary wedge pressure (PCWP) between 12 and 18 mm Hg. Cardiorespiratory variables were measured by a pulmonary artery catheter on the day of inclusion into the study and daily during the next 5 days. Gastric intramucosal pH (pHi) was measured by tonometry. Central venous pressure and PCWP were comparable within the subgroups (trauma/sepsis) throughout the entire study period. In the trauma patients, cardiac index (CI), oxygen consumption index (VO2I), and oxygen delivery index (DO2I), significantly increased only in the HES-treated patients. In the sepsis patients, CI, VO2I, and DO2I increased and remained higher than baseline only in the HES group (P < 0.01). Right ventricular ejection fraction (RVEF) was reduced (< 40%) in the HA patients and increased only in the HES patients (from 34% +/- 4% to 42% +/- 3%; P < 0.05). pHi remained normal (> 7.35) in both trauma groups and in the HES-treated sepsis patients. In the HA sepsis group, pH, decreased (> 7.20) within the study period (7.15 +/- 0.12 on Day 4), indicating deteriorated splanchnic perfusion. We conclude that long-term intravascular fluid therapy with HA in traumatized and sepsis patients has no advantages in comparison to LMW-HES. In both groups, volume replacement with HES even resulted in improved systemic hemodynamics. Decrease in pHi in the sepsis patients was blunted by HES infusion indicating improved splanchnic perfusion by this regimen of volume therapy.

Adult↗
PubMed1996

Platelet function and adrenoceptors during and after induced hypotension using nitroprusside.

BACKGROUND: Hypotension induced by sodium nitroprusside can minimize intraoperative blood loss. The release of endogenous catecholamines can influence adrenoceptors of platelets and thus might change the ability of platelets to aggregate. METHODS: Forty patients undergoing nasal septum, tympanoplastic, or sphenoid sinus surgery were randomly divided into two groups, those having controlled hypotension (A) and those serving as controls (B). Blood samples were drawn before the operation, after induction of anesthesia, 1 h after the start of the operation, and on the day after surgery. RESULTS: Epinephrine-induced platelet aggregation only increased in the controls on the day after surgery (A: from 49 +/- 25% to 47 +/- 29%; B: from 53 +/- 24% to 72 +/- 14%; mean +/- SD; P < 0.01). Spontaneous platelet aggregation increased in the controls from a median of 1.2 omega/h to 2.4 during the operation and 2.9 on the day after surgery but not after hypotension. On the day after surgery, alpha 2 receptors reached their maximum (A: 238 +/- 164; B: 234 +/- 80 per platelet). During the operation, the norepinephrine concentrations were significantly greater in group A (median, 419 pg/ml) than in group B (median, 217 pg/ml; P < 0.05). Blood loss was greater in the controls (A: 180 +/- 75; B: 379 +/- 120 ml; P < 0.05). CONCLUSIONS: Controlled hypotension using sodium nitroprusside reduces epinephrine-induced and spontaneous platelet aggregation. Even on the day after hypotension, the usual postoperative reactive increase in platelet aggregation did not occur. These results may be explained by the direct effect of nitroprusside on platelets, the augmented stress response, lower shear stress on platelets due to the lower blood pressure, or the decreased blood loss compared with the controls.

Adult↗
PubMed1996

Influence of long-term continuous intravenous administration of pentoxifylline on endothelial-related coagulation in critically ill patients.

OBJECTIVE: To determine the influence of pentoxifylline on endothelial-associated coagulation. DESIGN: Prospective, randomized, placebo-controlled study. SETTING: A surgical intensive care unit of a university hospital. PATIENTS: Consecutive patients (n = 60) with trauma or sepsis secondary to major (nontrauma) surgery. All patients received controlled mechanical ventilation. INTERVENTIONS: According to a randomized sequence, the patients either received pentoxifylline continuously over 5 days (1.5 mg/kg/hr iv) (trauma-pentoxifylline group [n = 15], sepsis-pentoxifylline group [n=15] or saline solution as placebo (trauma-control group [n = 15], sepsis-control group [n = 15]. MEASUREMENTS AND MAIN RESULTS: In addition to the standard coagulation screen, thrombomodulin, protein C, (free) protein S, and thrombin-antithrombin plasma concentrations were measured by enzyme-linked immunosorbent assays. Intensive care therapy, hemodynamics, and changes of Acute Physiology and Chronic Health Evaluation II score were comparable for pentoxifylline-treated and nontreated patients. An average dose of 2.5 g/day of pentoxifylline (range 2.2 to 2.9) was infused into the pentoxifylline-treated patients. At baseline, plasma thrombomodulin concentrations were higher in the septic patients than in the trauma patients. Thrombomodulin plasma concentrations increased significantly more in the control patients (trauma: from 38.9 +/- 10.5 to 59.9 +/- 10.1 ng/mL; sepsis: from 49.7 +/- 12.1 to 72.3 +/- 11.2 ng/mL) than in the pentoxifylline-treated patients (trauma: from 37.9 +/- 11.9 to 50.2 +/- 9.2 ng/mL; sepsis from 51.9 +/- 10.1 to 63.3 +/- 10.2). Starting from similar baseline values, protein C concentration increased significantly more in the sepsis-pentoxifylline patients (from 52.0 +/- 11.1% to 69.1 +/- 11.1%) than in the untreated septic patients (from 50.1 +/- 10.0% to 52.5 +/- 9.5%). There were no significant differences between the pentoxifylline-treated and nontreated groups for protein S and thrombin-antithrombin concentrations. Standard coagulation parameters (fibrinogen, activated partial thromboplastin time, antithrombin III) did not differ between these groups either. CONCLUSIONS: Continuous intravenous administration of pentoxifylline for 5 days beneficially influenced the thrombomodulin/protein C/protein S system in both the trauma and septic patients.

APACHE↗
PubMed1996

The influence of volume therapy and pentoxifylline infusion on circulating adhesion molecules in trauma patients.

Adhesion molecules appear to play a pivotal role in tissue damage secondary to the inflammatory process. Besides neutrophil- and endothelial-bound adhesion molecules, soluble forms have been detected in the circulating blood. They seem to be good markers of endothelial damage, but they may also have other biological functions. Plasma concentrations of soluble adhesion molecules (endothelial leucocyte adhesion molecules (sELAM-1), intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and granule membrane protein 140 (sGMP-140) were serially measured over 5 days by enzyme-linked immunosorbent assays (ELISA) in 45 consecutive trauma patients. These received, by random allocation, only either hydroxyethylstarch solution 10% (mean molecular weight 200,000 daltons) (n = 15) or human albumin 20% (n = 15) for volume therapy. Another 15 patients without defined volume therapy received pentoxifylline continuously (1.2 mg.kg-1.h-1). Measurements were carried out on the day of admission to the intensive care unit (baseline) and during the next 5 days. At baseline, plasma concentrations of all adhesion molecules were similar in all groups. In the hydroxyethyl starch group, sELAM-1 and sICAM-1 concentrations decreased significantly (p < 0.05) reaching normal values during the study period whereas the mean (SD) values increased in the pentoxifylline group (sELAM-1: 71.1 (16.7) to 91.6 (17.8) ng.ml-1) and the albumin group (sICAM-1: 400 (81) to 749 (101) ng.ml-1) (p < 0.05). sVCAM-1 increased outside the normal range only in the human albumin group (to 760 +/- 69 ng.ml-1) (p < 0.05). sGMP-140 plasma concentration increased only in those receiving albumin (432 (85) to 550 (93) ng.ml-1) and this was significantly different to the other groups (p < 0.05). None of the other haemodynamic or laboratory factors could be correlated with plasma concentrations of the adhesion molecules. We conclude that volume therapy with hydroxyethyl starch resulted in a decrease in circulating adhesion molecules in our trauma patients. In contrast, volume therapy with albumin did not exert this effect. Continuous infusion of pentoxifylline did not have a beneficial modulating action on circulating adhesion molecules.

Adult↗
PubMed1996

Isovolaemic haemodilution with hydroxyethylstarch has no effect on somatosensory evoked potentials in healthy volunteers.

BACKGROUND: An animal study in anaesthetized baboons demonstrated that somatosensory evoked potentials (SSEP) can be affected by extreme haemodilution. This might lead to misinterpretation and reduce the value of intraoperative SSEP monitoring when colloids are administered. In the present study, the effect of haemodilution (HD) and subsequent retransfusion of autologous blood on SSEP was determined in healthy non-premedicated volunteers. METHOD: Acute isovolaemic HD served as a model for blood loss immediately replaced with colloids. In 12 volunteers, 20 ml/kg.bw blood was withdrawn within 30 minutes and simultaneously multaneously replaced with 6% hydroxyethylstarch (HES). 30 minutes later, the autologous blood was retransfused within 30 minutes. Recording sites and parameters were: 1. Median nerve SSEP: cortical, cervical (C2), Erb's point; 2. Posterior tibial nerve SSEP: cortical, cervical (C2), lumbar (L1). In addition to SSEP latency and amplitude, median and tibial nerve central conduction times, spinal conduction time and nerve conduction velocity were determined. Serial SSEP measurements were made before, during and after HD and retransfusion every 15 minutes. RESULTS: HD consisting of a withdrawal volume of 1550 +/- 155 ml (mean +/- SD) induced a decrease in haematocrit from 42.0 +/- 3.1% to 29.6 +/- 1.6% (P < 0.001). Following retransfusion, haematocrit increased to 35.0 +/- 2.1% (P < 0.001). Neither HD nor retransfusion influenced SSEP parameters. CONCLUSION: We conclude from our data that the therapy of blood loss up to 30% of estimated blood volume with HES does not affect SSEP monitoring as long as normovolaemia is maintained.

Adult↗
PubMed1996

Can clonidine, enoximone, and enalaprilat help to protect the myocardium against ischaemia in cardiac surgery?

OBJECTIVE: To evaluate whether clonidine, enoximone, and enalaprilat reduce ischaemia-related myocardial cell damage in cardiac surgery. DESIGN: Prospective randomised controlled trial. SETTING: Clinical investigation in a cardiac anaesthesia department of a university hospital. PATIENTS: 88 consecutive patients undergoing coronary artery bypass surgery. INTERVENTIONS: After induction of anaesthesia patients continuously received the alpha 2 agonist clonidine (group 1, n = 22), the phosphodiesterase (PDE) III inhibitor enoximone (group 2, n = 22), the angiotensin converting enzyme (ACE) inhibitor enalaprilat (group 3, n = 22), or saline solution as placebo (control group, n = 22). The infusion was stopped immediately before the start of cardiopulmonary bypass. MAIN OUTCOME MEASURES: The ST segment was analysed and the activity of creatine kinase isoenzyme MB (CKMB), cardiac troponin T (TnT), and the BB isoenzyme of glycogen phosphorylase (GPBB) were measured before the start of infusion (baseline), after weaning from cardiopulmonary bypass (CPB), at the end of surgery, 5 h after CPB, and on the morning of the first and third postoperative days. RESULTS: Biometric data and time of cross-clamping were not significantly different in the four groups. Changes in the ST segment indicating ischaemia were least common in the enalaprilat group (P < 0.05). Postoperatively, CKMB activity was significantly higher in the clonidine and the control groups. Both new markers of myocardial cell damage increased more after CPB and postoperatively in the control patients (TnT peak: (mean (SD)) 3.99 (0.35) microgram/1; GPBB peak: 82 (15) ng/ml) and the clonidine-treated group (TnT peak: 3.80 (0.3) microgram/1; GPBB peak: 85 (14) ng/ml). Enalaprilat-treated patients showed the smallest overall changes in standard (CKMB) and new serological markers of myocardial ischaemia (TnT peak: 0.71 (0.1) microgram/1; GPBB peak: 44 (14) ng/ml). CONCLUSIONS: In patients treated with enalaprilat before CPB, both new, more sensitive markers of ischaemic myocardial tissue damage increased significantly less than in an untreated control group. Those treated with enoximone also had lower plasma concentration of TnT and GPBB than the control group, whereas clonidine did not reduce the concentration of these markers of myocardial ischaemia. Pharmacological interventions, such as the continuous infusion of the ACE inhibitor enalaprilat, before start of CPB may help to protect the heart against ischaemia/reperfusion injury.

Adrenergic alpha-Agonists↗
PubMed1996

Comparison of different prophylactic myocardium saving measures during heart surgery. Effects on perioperative troponin-T levels.

OBJECTIVE: Different prophylactic myocardium saving strategies are often routine in open heart surgery. Even if theoretically well established, they must be critically reviewed in times of limited financial resources. EXPERIMENTAL DESIGN: Troponin-T (TnT) is a valuable tool to detect even minor myocardial damages independently from concomitant muscle injuries. We measured intra- and postoperative TnT-values and ST-wave deviations on the ECG in a control group and in patients receiving one of the following prophylactic MEASURES: hypothermia during cardiopulmonary bypass (CPB), nitroglycerine ([0.5 microgram/kg/min]) or nifedipine [0.1 microgram/kg/min] after aortic cross-clamping until end of operation, or perioperative Mg2+ per os. PATIENTS AND SETTING: The study included 65 patients of a university hospital with preoperative good heart function scheduled for elective aorto-coronary bypass operation. RESULTS: TnT values increased in all groups after CPB and peaked between end of operation and first post-operative day. TnT values above the critical border of 1.0 microgram/l in the early period after CPB were less often seen in the nitroglycerine and nifedipine group. No pronounced differences could be observed after the first postoperative day. Patients of the hypothermia group had most often TnT values above 1.0 microgram/l. Maximum TnT values of the control, the hypothermia and the Mg(2+)-group correlated with the duration of aortic-crossclamping. No correlation existed between ST-deviations and TnT-values. CONCLUSIONS: The prophylactic measures failed to reduce myocardial damage as evidenced by the course of TnT values. They can therefore not be recommended as routine strategies in patients with good left heart function. Especially hypothermia should be considered carefully.

Aged↗
PubMed1996

[Effects of sevoflurane on the area of the liver and spleen].

Recently, there has been increased interest in the preservation of hepatic function during anaesthesia and surgery. In common with other halogenated volatile anaesthetics, sevoflurane causes dose-related cardiovascular depression, which suggests that the blood flow of various organ systems is affected. This paper summarises some of the published work dealing with sevoflurane and alterations of splanchnic and hepatic blood flow to date, mostly from animal studies. However, the experience with this substance in human studies is small as yet, and previously investigated animal models are too different to compare to humans. The effort should be encouraged to study this new volatile anaesthetic in human subjects; if a parallel to isoflurane can be drawn, the impact of both substances on the hepatic circulation should be quite small. In Germany, the introduction of sevoflurane into clinical practice should be a reason to proceed with clinical investigations of this type.

Anesthetics, Inhalation↗
PubMed1996

[Changes in somatosensory evoked potentials after sevoflurane and isoflurane. A randomized phase III study].

Monitoring of somatosensory evoked potentials (SEP) is used to identify critical phases of cerebral ischaemia by means of characteristic changes in the signal patterns. A correct interpretation of the results is possible, however, only if the influence of drugs that act on the central nervous system is known. We were able to show that volatile anaesthetics have an impact on latencies and stimulus amplitudes. In this study, we examined the influence of sevoflurane as compared with isoflurane on the conduction of SEP by the median nerve at various concentrations. In addition, we determined how the addition of nitrous oxide (N2O) influenced the stimulus response of median-nerve SEP. Both isoflurane and sevoflurane caused a dose-dependent increase in latency of the primary cortical complex, while the influence on the cervical components of the SEP with respect to increased latency was only slight. No significant difference was found between both study groups. Under the influence of N2O, there were marked reductions in amplitude of the cortical stimulus response. Thus, it can be recommended that supplementation with N2O should be avoided in the presence of low initial amplitudes. Based on our results, the use of isoflurane and sevoflurane concentrations up to 1.0 MAC seems to be compatible with intraoperative monitoring of SEP.

Anesthetics, Inhalation↗
PubMed1996

Effects of pipecuronium and pancuronium on cerebrospinal fluid pressure in neurosurgical patients.

Arterial hypertension and/or tachycardia may alter intracranial pressure in neurosurgical patients. We compared the effects of pancuronium 0.1 mg/kg and pipecuronium 0.1 mg/kg given as i.v. bolus on cerebrospinal fluid (CSF) pressure in 2 groups of 10 patients each scheduled for intracranial surgery in the supine position. Before surgery, no patient presented clinical symptoms of elevated intracranial pressure (ICP). Anesthesia was induced and maintained with fentanyl and midazolam. Ventilation with 50% nitrous oxide in oxygen was adjusted to maintain arterial pCO2 at 30-35 mmHg. After induction of anesthesia, CSF pressure was registered via a lumbar subarachnoid catheter before and 3, 5, 10, and 30 min after pipecuronium or pancuronium administration. Hemodynamics were monitored using radial and pulmonary artery catheters. All variables underwent analyses of variance for repeated measures with p < 0.05 considered significant. Mean CSF pressure decreased insignificantly from 15 +/- 5 mmHg (before injection) to 14 +/- 4 mmHg in patients given pipecuronium and from 13 +/- 4 mmHg to 10 +/- 3 mmHg in the pancuronium group without significant differences between the study groups. Heart rate and arterial pressure increased significantly (p < 0.001) in patients given pancuronium but remained stable after pipecuronium. Onset and duration of neuromuscular blockade were comparable between groups. Based on our results, pipecuronium is a safe alternative to pancuronium during neurosurgical procedures in patients without abnormally high intracranial pressure.

Adult↗
PubMed1995

Effects of intravenous anesthetic agents on middle cerebral artery blood flow velocity during induction of general anesthesia.

OBJECTIVE: Our objective was to quantify the effects of intravenous anesthetics on values measured by or derived from transcranial Doppler sonography (TCD) during induction of general anesthesia. METHODS: We recorded blood flow velocity in the middle cerebral artery (V-MCA) before, during, and after induction of general anesthesia in six groups of young patients without intracranial pathology (n = 10 each) using TCD. Patients were randomized to receive either 2 mg/kg propofol, 1.5 mg/kg methohexital, 5 mg/kg thiopental, 0.3 mg/kg etomidate, 2 micrograms/kg fentanyl and 0.15 mg/kg midazolam, or 1.5 mg/kg ketamine and 0.15 mg/kg midazolam intravenously. At 2 min after injection, each patient was intubated and given isoflurane 0.8% and nitrous oxide 66% in oxygen. Ventilation was set to achieve an end-tidal PCO2 of 40 mm Hg. V-MCA, arterial blood pressure, heart rate, hematocrit, and PCO2 (venous samples) were measured before and 1, 3, 5, 10, and 30 min after induction of anesthesia. RESULTS: The preinduction data were not different between groups. At 1 min after injection, propofol, thiopental, methohexital, and etomidate significantly decreased V-MCA. TCD values were only slightly affected following fentanyl/midazolam. Ketamine/midazolam induced a modest rise in V-MCA. After endotracheal intubation, V-MCA increased in all groups, and slowly declined thereafter. CONCLUSIONS: Under the circumstances of our study, values derived from TCD measurements responded differently to the agents used to induce general anesthesia in nonneurosurgical patients.

Adult↗
PubMed1995

Alterations in circulating vasoactive substances in the critically ill--a comparison between survivors and non-survivors.

OBJECTIVE: Regulation of circulatory homeostasis is based on several factors including various circulating vasoactive substances. Whether these regulators differ between survivors and non-survivors was investigated in critically ill patients. DESIGN: Prospective study. SETTING: Clinical investigation on a surgical intensive care unit of an university hospital. PATIENTS: 60 consecutive patients suffering from trauma (n = 21) or postoperative complications (n = 39) were studied prospectively. The patients were divided into survivors (n = 27) and non-survivors (n = 33). Therapy was adjusted to the standards of modern intensive care management by physicians who were not involved in the study. MEASUREMENTS AND RESULTS: Endothelin-1, atrial natriuretic peptide (ANP), vasopressin, renin, and catecholamine (epinephrine, norepinephrine) plasma levels were measured from arterial blood samples using radioimmunoassay (RIA) or high-pressure liquid chromatography (HPLC) technique on the day of admission to ICU and during the following 5 days. Various hemodynamic parameters were also monitored during that period. The non-survivors showed elevated pulmonary artery pressure (PAP: 34.1 +/- 5.4 mmHg) and pulmonary capillary wedge pressure (PCWP: 20.3 +/- 7.3 mmHg) already at the beginning of the study. Cardiac index (CI) did not differ among the groups, whereas right ventricular ejection fraction (RVEF) decreased in the non-survivors. PaO2/FIO2 decreased only in the non-survivors, whereas VO2 increased in the survivors (from 246 +/- 48 to 331 +/- 43 ml/min). Plasma levels of renin (from 206 +/- 40 to 595 +/- 81 pg/ml) and vasopressin (from 5.78 +/- 0.82 to 7.97 +/- 0.69 pg/ml) increased significantly in the non-survivors. Epinephrine and norepinephrine plasma concentrations were elevated in the non-survivors already at baseline and tremendously increased in these patients during the following days. ANP plasma levels significantly increased also only in the non-survivors (from 188 +/- 63 to 339 +/- 55 pg/ml) (p < 0.05). Endothelin-1 decreased in the survivors, whereas it significantly increased in the non-survivors (from 3.62 +/- 0.68 to 9.37 +/- 0.94 pg/ml) during the study period (p < 0.05). Analyses of co-variance revealed overall no significant correlation between circulating vasoactive substances and hemodynamics. CONCLUSIONS: Systemic and regional regulators of the circulation were markedly changed by critical illness. In survivors, these regulators almost normalized within the study period of 5 days, whereas in non-survivors these alterations were even aggravated. It can only be speculated whether these regulator systems were influenced by activation of various mediator systems or whether they themselves influenced the negative outcome in the non-survivors.

APACHE↗
PubMed1995

Thrombomodulin in intensive care patients.

OBJECTIVE: Changes of endothelial-related coagulation was studied in intensive care patients. DESIGN: Descriptive, prospective. SETTING: Clinical investigation, intensive care unit of an university hospital. PATIENTS: 40 consecutive critically ill patients with severe trauma (n = 20) or postoperative complications (n = 20) were studied. 14 patients suffered from sepsis, 12 patients suffered from acute renal failure. INTERVENTIONS: 12 patients with acute renal failure were continuously hemofiltrated. All patients were on continuous sedation (fentanyl and midazolam) and mechanical ventilation. MEASUREMENTS: In addition to standard coagulation variables, thrombomodulin (TM), protein C and protein S as well as thrombin/antithrombin III (TAT) plasma concentrations were measured from arterial blood samples using enzyme-linked immuno-sorbent assays (ELISA). Measurements were carried out on the day of admission (trauma patients) or on the day of diagnosis of sepsis and during the next 4 days. MAIN RESULTS: Throughout the entire investigation period, TM plasma concentrations in patients with sepsis (baseline: 90 +/- 25 micrograms/l, 4th day: 152 +/- 28 micrograms/l) were significantly higher than in non-septic patients (baseline: 60 +/- 29 micrograms/l, 4th day: 42 +/- 15 micrograms/l). 15 of the 40 patients died within or after the end of the investigation period. TM plasma concentrations of survivors were lower (maximum: 63 +/- 18 micrograms/l) than in the non-survivors (maximum: 159 +/- 22 micrograms/l) (p < 0.05). Hemofiltered patients showed higher TM plasma levels, which further increased during the hemofiltration procedure. Protein C and (free) protein S were without significant group differences. TAT plasma levels were elevated above normal in all patients (no group differences). CONCLUSIONS: Besides plasmatic and platelet-related coagulation, endothelium-associated coagulation appears to be also important for maintenance of hemostasis. TM plasma concentrations were elevated in all our critically ill patients, particularly when sepsis was evident. This appears to be most likely due to endothelial membrane damage with increased release of membrane-bound TM into the circulating blood in these patients. The importance of the elevated plasma levels of circulating soluble TM on hemostasis in these patients is an ongoing debate and warrants further studies.

Adult↗
PubMed1995

[Anesthesia for heart transplantation in newborn and suckling infants. Special aspects of the hypoplastic left heart syndrome].

Paediatric cardiac transplantation (pHTX) has gained widespread acceptance as a therapy in end-stage myocardial failure and some forms of congenital heart disease, particularly hypoplastic left heart syndrome (HLHS). The major problems to the anaesthesiologist in these patients are induction of anaesthesia in infants with HLHS and treatment of pulmonary hypertension in the early post-bypass period. PATIENTS AND METHODS. Anaesthesia for pHTX was performed in 15 children < 1 year of age (4-237 days); 12 suffered from HLHS, 2 from endocardial fibroelastosis, and 1 from dilatative cardiomyopathy. Induction of anaesthesia in patients with HLHS IS a challenge to the anaesthesiologist, as he has to maintain the delicate balance between pulmonary and systemic blood flow. Anaesthesia was induced with fentanyl (10-15 micrograms/kg) and pancuronium (0.2-0.4 mg/kg) and maintained with fentanyl (total dosage 70-100 micrograms/kg). Modification of ventilatory parameters such as FiO2, PaCO2, and airway pressure (PEEP, I:E ratio) was used to influence systemic and pulmonary blood distribution in the pre-bypass period according to changes in haemodynamics (target: O2 saturation approximately 75%-80%, PaCO2 45-50 mmHg). Treatment of pulmonary hypertension in the weaning and early post-bypass period consisted of respiratory (PaCO2 < 30 mmHg) and metabolic alkalinisation (pH 7.45-7.55, BE > +3 mmol/l), the use of prostaglandin E1 (3-6-12 micrograms/kg.h), and the phosphodiesterase inhibitor enoximone (10-15 micrograms/kg.min). Additional positive inotropic support was achieved with dobutamine (5-10 micrograms/kg.min), adrenaline (0.1-0.5 micrograms/kg.min), and/or orciprenaline (0.1-0.2 micrograms/kg.min) and calcium chloride (25-100 mg/kg). RESULTS. Two children died intraoperatively and 1 on the 1st postoperative day from overwhelming pulmonary vascular resistance and right ventricular failure. Three children died between 3 and 4 weeks postoperatively, 1 from cytomegalovirus infection, 1 from sepsis, and 1 from acute rejection. Nine patients survived and are well up to 5.5 years after transplantation. CONCLUSION. Pulmonary hypertension in the weaning and early post-bypass period is the main anaesthesiological problem of pHTX, particularly in children with HLHS. A polypragmatic approach to this problem consisting of alkalinisation, pulmonary vasodilatation, and inotropic support is presented and seems to be effective. Further improvements in concepts of pHTX are limited by the lack of donor organs. Though the experience with pHTX in neonates and infants is growing slowly, it might be a routine procedure from the anaesthesiological point of view within a few years in some selected centres.

Anesthesia↗