Procalcitonin for early prediction of survival outcome in postoperative critically ill patients with severe sepsis.

BACKGROUND: Identification of postoperative patients at high risk of dying early after intensive care unit (ICU) admission through a fast and readily available parameter may help in determining therapeutic interventions or further diagnostic procedures that could have an impact on patients' outcome. The aim of our study was to assess the utility of procalcitonin (PCT) and other readily available parameters, as useful early (days 1-3) predictors of mortality in postoperative patients diagnosed with severe sepsis within 24 h preceding their operation. METHODS: More than a period of 2 yr, subsets of 69 postoperative patients admitted with severe sepsis and 890 non-septic ICU patients were investigated. PCT, C-reactive protein (CRP) and sequential organ failure assessment (SOFA) score were recorded over the duration of ICU stay. RESULTS: PCT area under receiver operating characteristic (ROC) curve was 0.78 on day 3 and was highly predictive of fatal outcome (0.90) at day 6. Area under ROC curve of SOFA score was 0.85 on day 3 and remained in this range until day 6. Area under ROC curves on day 3 of CRP (0.61) was non-predictive and remained non-predictive over the duration of ICU stay. CONCLUSIONS: PCT exhibited no discriminative power early after ICU admission for prediction of mortality in critically ill patients with severe sepsis, compared with a high predictive power of SOFA score on day 3. However, using PCT could still serve as a useful complementary comparator for prediction of survival outcome using the SOFA score.

[Anesthesia related physiologic and pharmacologic changes in the elderly]. / Anästhesierelevante physiologische und pharmakologische Veränderungen im Alter.

The importance of geriatric patients is growing with the increasing number of people over the age of 65 and with the higher percentage of surgical interventions. Multiple physiological changes in the cerebrovascular, cardiovascular, respiratory, renal and hepatic system, and pharmacological changes such as a reduction in hydrophilic distribution and metabolism cause increased drug sensitivity, a reduced elimination rate and prolonged duration of action. Pre-existing diseases correlate with an increased rate of complications such as hypoxia, hypothermia and cardiovascular, pulmonary, cerebral or renal complications, the highest incidence of which occurs on the first and between the third and fifth postoperative days. To reduce the incidence of these complications, a thorough pre-anaesthetic examination and optimization of the patient's condition is recommended. Hypovolaemia or too intense premedication should be avoided. In cardiac-risk patients, a beta-adrenergic blockade is necessary. Purely regional anaesthesiological techniques should be used as they reduce one-month mortality by a third and morbidity by up to 59%. For general anaesthesia, preoxygenation and careful titration of the drugs used help to achieve cardiovascular stability. Institutionalized postanaesthetic standards help to avoid an aggravation of the patient's condition due to shivering, hypothermia or postoperative pain.

Procalcitonin and proinflammatory cytokine clearance during continuous venovenous haemofiltration in septic patients.

Procalcitonin (PCT), interleukin-6 (IL-6), tumour necrosis factor a (TNFalpha), and interleukin-1beta (IL-1beta) are important clinical prognostic markers in ICU septic patients. The goal of the study was to determine whether continuous venovenous haemofiltration (CWH), using an AN69 haemofilte, leads to elimination of PCT, TNFalpha, IL-6 and IL-1beta in 13 septic patients with multi-organ failure. At the start of haemofiltration (0), 6 and 12 hours the mean afferent plasma concentration +/- SD of PCT (10.1 +/- 9.1, 7 +/- 6, 5.9 +/- 5.7 ng/ml), IL-6 (804.6 +/- 847.6, 611.7 +/- 528.4, 575.2 +/- 539.2 pg/ml), and that of TNFalpha (4.5 +/- 2.6, 4 +/- 3.1, 3.8 +/- 2.9 pg/ml) significantly declined during CVVH. The efferent plasma concentrations were significantly lower than the corresponding afferent concentrations. PCT; IL-6 and TNFalpha were detectable in the ultrafiltrate of all patients. IL-1beta was only detectable in the plasma of eight patients and the ultrafiltrate of five patients. The plasma clearance of PCT, IL-6 and TNFalpha significantly decreased after 12 hours as a result of a decline in the adsorptive elimination of the mediators due to progressive membrane saturation. We demonstrated that if PCT, IL-6 and TNFalpha are used as clinical prognostic markers in septic patients who are treated with CWIH using an AN69 membrane, one should be aware that their plasma level could be modified by the therapy. In addition CWH could represent an appropriate tool to remove a broad spectrum of proinflammatory mediators, if such removal is required in septic patients.

Two propofol formulations are equivalent in small children aged 1 month to 3 years.

BACKGROUND: Propofol has been widely used in general anesthesia. Although it is also often used in pediatric anesthesia, there has been only limited scientific evidence on the use of propofol in children up to 3 years. METHODS: A prospective, randomized, double-blind, therapeutic equivalence study comparing two propofol 1% emulsions (Propofol 1% Fresenius vs. Diprivan 1%) was performed in 60 patients scheduled for routine surgery or for diagnostic laparoscopic procedures requiring anesthesia. To guarantee comparability of age distribution between the two groups, a stratified randomization with patients younger than 12 months of age in a low age group and with patients aged 12 months to 3 years in a high age group was used. The average propofol induction dose and the average propofol infusion dose were analyzed to prove equivalence. The side-effects profile was analyzed to compare the safety profiles of the two propofol formulations in this study. RESULTS: There were no differences in baseline characteristics between the two treatment groups of high and low age. Medications used for induction and maintenance of anesthesia, and side-effects profiles were comparable, as were the average propofol dose for induction of anesthesia (range of the mean dose 4.0-4.2 mg/kg) and for maintenance of anesthesia (range of the mean dose in the first hour 8.74-9.42 mg x kg(-1) x h(-1)). CONCLUSIONS: The two 1% propofol formulations were equally effective in our patient population of infants and young children between 1 month and 3 years of age. No differences between the two propofol formulations were found with regard to the circulatory reaction, lipid metabolism, dosages, and recovery profile in the studied age groups.

Antithrombin III in patients with severe sepsis: a pharmacokinetic study.

OBJECTIVES: To evaluate the safety, pharmacokinetics, and the practicability of two different antithrombin III (AT III) high-dose regimens in patients with severe sepsis. DESIGN: Prospective, open, randomized, 2 parallel groups, multinational clinical trial. SETTING: Eleven academic medical center intensive care units (ICU) in Austria, Belgium, Denmark, Germany, Norway and Sweden. PATIENTS: Thirty-three patients with severe sepsis who received standard supportive care and antimicrobial therapy, in addition to the administration of AT III. INTERVENTIONS: Patients received an intravenous loading dose of 6,000 IU AT III followed by either intermittent bolus infusions of 1,000 IU AT III every 4 h or a continuous infusion of 250 IU AT III/h for 4 days, resulting in a total dose for both dosage regimens of 30,000 IU AT III. MEASUREMENTS: All patients were evaluated for safety and all but one for pharmacokinetics. RESULTS AND CONCLUSIONS: The administration of AT III was safe and well tolerated. The overall 28-day all-cause mortality was 30% (43% intermittent bolus infusions; 21% continuous infusion). The mean probability of dying according to the SAPS II was 48%. The difference in mortality between both groups was within the range of chance. AT III plasma levels were elevated from low baseline levels to above 120% soon after onset of AT III therapy and remained at these levels for the treatment phase of 4 days. Functional and immunologic levels of AT III corresponded very well. With an overall median volume of distribution of 4.5 l (range: 2.4-6.5 l), AT III only moderately extended beyond plasma. The overall median elimination half-life was 18.6 h (range: 5.1-37.4). Overall, median response was 1.75% per IU/kg (range: 1.14-2.8). The variability of elimination parameters was quite noteworthy (CV = 41-59%), whereas distribution-related parameters showed a moderate variability (CV = 24%). In spite of this variability, both high-dose IV regimens reliably provided AT III levels above 120% for all but one patient. An increased mortality was observed for patients with a distribution volume exceeding 4.5 l (or a response < 1.7% per IU/kg). AT III distribution volumes above 4.5 l might indicate a capillary leak phenomenon. The continuous infusion regimen was slightly preferred by the investigators with regard to practicability.

Comparison of a new piezoelectric train-of-four neuromuscular monitor, the ParaGraph, and the Relaxometer mechanomyograph.

The ParaGraph is a new device for monitoring neuromuscular function using a piezoelectric motion sensor. In 20 patients, monitoring of neuromuscular block produced by cisatracurium 0.1 mg kg-1 was compared using the ParaGraph and a Relaxometer 2 mechanomyograph. The ParaGraph was quick to set up, and easy to operate and interpret. There were no significant differences in the time to 100% depression of T1/T0, time to 25% recovery of T1/T0 or time to recovery of T1/T0 from 25% to 75%, measured by the two monitors. When the difference between the two monitors was plotted against the average of the two measurements, the limits of agreement for T1/T0 (-42.95, +53.98%) and the train-of-four ratio, T4/T1 (-0.28, +0.21) were too wide to allow the values given by the two monitors for individual patients to be used interchangeably.

Total intravenous anesthesia with remifentanil, propofol and cisatracurium in end-stage renal failure.

PURPOSE: To compare recovery parameters of total intravenous anesthesia (TIVA) with remifentanil and propofol, hemodynamic responses to perioperative events, and pharmacodynamic parameters of cisatracurium in 22 end-stage renal failure and 22 normal renal function patients. METHODS: Anesthesia was induced with 2-3 mg x kg(-1) propofol and 1 microg x kg(-1) remifentanil and maintained with 75 microg x kg(-1) x min(-1) propofol and propofol initial infusion of 0.2 microg x kg(-1) x min(-1) propofol. Arterial pressure and heart rate were maintained by remifentanil infusion rate adjustments. The first twitch (T1) was maintained at 25% by an infusion of cisatracurium. RESULTS: There was no difference in the time to maintenance of adequate respiration, date of birth recollection, first analgesic administration, between the renal failure (4.8+/-2.5, 7.8+/-3.2, 12.3+/-5.3 min respectively) and the control group (5.2+/-2.8, 8.1+/-3.1, 12.7+/-5.5 min): nor were there any differences in the time to 25% T1 recovery, T1 recovery from 25% to 75%, or cisatracurium infusion rate between the renal failure group (32.1 +/-10.8 min, 18.2+/-5.5 min, 0.89+/-0.29 microg x kg(-1) min(-1) respectively) and the control group (35.9 (7.9 min, 18.4+/-3.8 min, 0.95+/-0.22 microg x kg(-1) x min(-1)). CONCLUSION: End-stage renal failure does not prolong recovery from TIVA with remifentanil and propofol, or the recovery from cisatracurium neuromuscular block.

[Hypertonic-hyperoncotic solutions: possibilities and limits]. / Hypertone-hyperonkotische Lösungen: Möglichkeiten und Grenzen.

Hypertonic-hyperoncotic solutions are a supplementary possibility in the acute treatment of hypovolemia. The main mechanism of action of this solution is, induced by the tonicity of the infusion (approximately 2400 mOsm/l), the transcapillary fluid shift from the intracellular and interstitial to the intravascular compartment. Additionally the fluidity of blood is improved (due to an increase in the diameter of the capillaries), the adherence of leucocytes to the endothelial wall is reduced, and the arteriolar vasomotion is restarted. Due to the available prehospital and clinical results it can be concluded, that hypertonic-hyperoncotic solutions offer advantages compared to conventional fluid therapy regimes: rapid stabilization of hemodynamics, reduction of posttraumatic volume deficiency, of posttraumatic edema and of posttraumatic complications and an improvement of the outcome of the patients. If the therapeutic recommendations are followed, such as a dose of 4 ml/kg body weight, infusion time of about 3-5 minutes and after the end of the infusion application of colloids or crystalloids in an amount as needed, no side effects will occur. Only immediately after the end of infusion sodium, chloride and osmolarity will slightly increase, however these parameters will normalize within the first posttraumatic day. Hypertonic-hyperoncotic solutions are trigger-solutions, as with the infusion of these types of solution it is possible to restore hemodynamics adequately and to prevent shock-induced complications.

[Karl E. Hammerschmidt. Humanist, natural scientist and pioneer in anesthesia]. / Karl E. Hammerschmidt. Humanist, Naturwissenschaftler und Narkosepionier.

Karl Eduard Hammerschmidt was born in Vienna in 1801. There are indications that after studying law he passed on to studies in medicine and surgery in Vienna, though it has to be said there is no trace of his attaining any qualification. After this he worked in various scientific sectors and in recognition of his achievements he was accepted as a member of the Kaiser Leopold Academy of Researchers in Natural Sciences in Bonn. From February 1847 to March 1848 he induced numerous general anaesthetics with ether, working with Dr. J. Weiger, a dentist in Vienna. On 11 July 1847 he published preliminary statistics based on 1560 dental operations performed under ether anaesthesia and also on numerous experiments performed on himself and investigations conducted with ether in animals and in healthy subjects. From the viewpoint of scientific research into and widening of the applications of ether anaesthesia, his most meritorious achievements include the early publication of a staging classification for ether anaesthesia, the introduction of an anaesthetic protocol for patients that also lent itself to data recording for statistical purposes and the early realization that the ability to hear is retained for a very long time during anaesthesia. In 1848 Hammerschmidt was obliged to flee to Istanbul by way of Hungary because of his involvement in the October Revolution. Once there, he continued to work as a doctor and later became Professor of Medicine at the University of Istanbul. He converted to Islam, taking the name of Abdullah Bey, and also became a colonel in the Turkish army. He was one of the founders of the Red Crescent, the humanitarian sister organization of the Red Cross, and the Turkish Post commemorated this with the issue of a stamp honouring him when the organization celebrated the centenary of its formation in 1968. In 1869 the Hapsburg dynasty also honoured him with orders and distinctions. He died in Istanbul in 1874 as a highly esteemed personage.

Perioperative ventricular dysrhythmias in patients with structural heart disease undergoing noncardiac surgery.

UNLABELLED: Noncardiac surgical patients with preoperative ventricular dysrhythmias and structural heart disease may be at increased risk of adverse cardiac outcome. We evaluated how anesthesia and surgery affect the course of ventricular dysrhythmias (premature ventricular beats [PVB] and repetitive forms of ventricular beats [RFVB]: couplets and nonsustained ventricular tachycardia) noted preoperatively in patients with structural heart disease and whether the frequency of ventricular dysrhythmias affects cardiac outcome. In a prospective study, 70 patients scheduled for noncardiac surgery with structural heart disease and RFVB on preoperative Holter electrocardiogram were continuously monitored intraoperatively and for 3 days postoperatively. Holter tracings were analyzed for rhythm, medians of total PVB and RFVB per hour. Preoperative RFVB recurred intraoperatively in 35% and postoperatively in 87% of patients. There was a significant intra- and postoperative decrease of total PVB per hour (P < 0.05) and RFVB per hour (P < 0.01). Frequency of ventricular dysrhythmias in the five patients suffering adverse outcome (unstable angina, n = 1; congestive heart failure, n = 4) did not significantly differ from those with good outcome. We conclude that in noncardiac surgical patients with structural heart disease and RFVB, the frequency of ventricular dysrhythmias is not associated with adverse cardiac outcome. IMPLICATIONS: Using continuous electrocardiogram monitoring, we investigated whether the frequency of perioperative ventricular dysrhythmias independently affects outcome in patients with structural heart disease undergoing noncardiac surgery. The incidence of perioperative dysrhythmia in patients with an adverse outcome (8%) did not differ from those with a good outcome.

Iatrogenic ruptures of the tracheobronchial tree.

We did a retrospective study in 12 patients with iatrogenic tracheal or tracheobronchial ruptures treated since 1975. Ten female subjects, one male subject, and one child (age range, 8 to 72 years), all of whom had undergone intratracheal intubation, were admitted to the hospital. Four patients had been intubated with a double-lumen catheter (two Carlens type with carinal spur, two Robertshaw without spur), and seven had had "high volume-low pressure" tubes, placed under emergency conditions in three of those seven cases. In one further case, an unsuccessful attempt of percutaneous tracheostomy had been made. The localization of the ruptures (all of them longitudinally in the membranaceous wall; length, 2 to 13 cm; mean, 7 cm) comprised both cervical and intrathoracic trachea in seven, the intrathoracic trachea in three instances, and the left main stem bronchus in two cases. Ten patients had mediastinal and subcutaneous emphysema, seven presented with a pneumothorax, and nine had intratracheal bleeding. The interval until the onset of symptoms and diagnoses differed widely: twice diagnoses were made intraoperatively, during thoracic surgery. The longest interval until diagnosis was 5 days; only then did the patient show subcutaneous emphysema and have retrosternal pain. All patients had surgical repair. Nine recovered without sequelae, and three died of septic multiorgan failure.

[The anesthesiologic risk patient. Preoperative evaluation, intraoperative management and postoperative monitoring]. / Der anaesthesiologische Risikopatient. Präoperative Evaluierung, intraoperatives Management und postoperative Uberwachung.

A high-risk patient is a challenge to the anaesthesiologist. If surgical intervention is indicated the perioperative anaesthesiological management has to be carefully adapted to the requirements of the patient. If the patient is classified a high-risk at the preoperative anaesthesiological assessment, the therapeutic management has to aim at optimizing the patient's preoperative physical status. Intraoperatively, the minimal monitoring standards have to be extended by addition of specific non-invasive or invasive monitoring techniques to observe the intraoperative cardiovascular or pulmonary function according to the patient's preoperative disease. There are no recommendations about the choice of the anaesthesia techniques; the decision for general or regional anaesthesia depends on the site of operation and is guided by the individual experience of the anaesthesiologist. During the postoperative period each high-risk patient has to be observed in the intensive care unit to continue intraoperative monitoring and therapy. Patients at risk of postoperative myocardial ischaemia or infarction should be closely monitored for 3-5 days postoperatively. The perioperative risk of morbidity and mortality associated with elective surgical procedures has to be evaluated for each patient and the risk-benefit analysis discussed in a interdisciplinary dialogue involving the surgeon, the patient and the patient's family.

Pain treatment in the ICU: intravenous, regional or both?

Adequate treatment of pain in ICU patients should be an integral part of ICU management, as inadequately treated pain leads to a series of complications that may counteract the success of ICU treatment. For continuous intravenous use we recommend sufentanil in a dose of 0.75-1.0 microgram kg-1 h-1 in mechanically ventilated patients and in a dose of 0.25-0.35 microgram kg-1 h-1 in intubated and spontaneously breathing patients. On-demand analgesia, administered via the intravenous or epidural route, may be an alternative to a relatively fixed continuous infusion of an analgesic drug, and in some ICU patients the transdermal use of opioids can be an alternative to continuous intravenous drug application or PCA. Increased sizes of the patch (25, 50, 75, 100 cm2) provide sustained transdermal rates of approximately 25, 50, 75 and 100 micrograms h-1 of fentanyl over a period up to about 72 hours. Patients with trauma to the thorax, pelvic fracture, or after major surgical interventions will be better managed by regional application of analgesic drugs alone or in combination with a systemic analgesic drug infusion. To achieve the best results it is necessary to be well informed and trained in the method, to know the advantages and disadvantages, the correct and modified dosages of the drugs used, and the indications and contraindications.