Search

Background: To evaluate the concept of critical illness-related corticosteroid insufficiency (CIRCI) by studying the clinical significance, in terms of risk factors and outcome, of changes in the cortisol response to repeated adrenocorticotropic hormone (ACTH) testing in the course of critical illness., Patients and Methods: In a retrospective study in a medical-surgical intensive care unit (ICU) of a university hospital, we retrospectively included 54 consecutive patients during a 3-year period, who underwent 2 conventional 250 μg ACTH tests at an interval >24 hours, because of ≥6 hours hypotension requiring repeated fluid challenges or vasopressor/inotropic treatment, while corticosteroid treatment was not (yet) initiated. Serum cortisol was measured immediately before and 30 and 60 minutes after intravenous injection of 250 μg of ACTH. Patients were divided into those with an increase (≥0, n = 27) or a decrease (n = 27) in time in delta (Δ) cortisol in response to ACTH and with a Δcortisol <100 (n = 11) and ≥100 nmol/L (n = 43) at the second ACTH test., Results: Changes in Δcortisol in time were paralleled by changes in Δcortisol/albumin, with a higher frequency of septic shock, persistently high disease severity, increased renal replacement therapy, and decreased platelet counts in the course of disease with a decrease in Δcortisol in time. Similar trends in increased disease severity were observed when Δcortisol remained or fell to <100 nmol/L. A decrease in Δcortisol between the 2 tests, particularly to <100 nmol/L, was associated with increased mortality (18 nonsurvivors in the ICU)., Conclusions: The findings favor the concept of dynamic adrenal function rather than poor reproducibility of the ACTH test, so that development of CIRCI, particularly in complicated septic shock and indicated by a fall in Δcortisol (to <100 nmol/L) upon ACTH, correlates to a poor prognosis, independently of baseline cortisol, cortisol binding in blood, and disease severity.

Background: In 2007 a national guideline on perioperative nutrition was issued in the Netherlands. As external indicator for adequacy of nutritional therapy, the percentage of malnourished patients who reach at least 1.2 grams of protein on day 4 after admission was chosen by the Netherlands Health Care Inspectorate., Methods: We developed an algorithm that allows users to ask for advice on which artificial nutritional formula to prescribe and at which rate, assuring provision of adequate amounts of both protein and energy. Feedback on nutritional therapy is given to the users on a daily basis, and to the management per quarter. Both the advice and the feedback have been integrated in our data management system. The advice module is also available on-line., Results: In the baseline situation over the first four quarters (2006) an average of 30.2% of patients who had a full day 4 in our unit reached the protein indicator. In the last six quarters post-implementation, the average percentage reached was 56.5% with values consistently over 50%. Changes were statistically significant at third quarter of 2007 (p<0.05) and thereafter (p<0.001). Results for day 7 of admission were unaffected, which indicates that targets were reached earlier during hospital stay., Conclusion: Our study shows that integration of nutritional advice and automatically generated feedback to users in a data management system consistently improves delivery of (early) nutrition.

Introduction: Optimal nutrition for intensive care patients has been proposed to be the provision of energy as determined by indirect calorimetry, and protein provision of at least 1.2 g/kg pre-admission weight per day. The evidence supporting these nutritional goals is based on surrogate outcomes and is not yet substantiated by patient oriented, clinically meaningful endpoints. In the present study we evaluated the effects of achieving optimal nutrition in ICU patients during their period of mechanical ventilation on mortality., Methods: This was a prospective observational cohort study in a mixed medical-surgical, 28-bed ICU in an academic hospital. 243 sequential mixed medical-surgical patients were enrolled on day 3-5 after admission if they had an expected stay of at least another 5-7 days. They underwent indirect calorimetry as part of routine care. Nutrition was guided by the result of indirect calorimetry and we aimed to provide at least 1.2 g of protein/kg/day. Cumulative balances were calculated for the period of mechanical ventilation. Outcome parameters were ICU, 28-day and hospital mortality., Results: In women, when corrected for weight, height, Apache II score, diagnosis category, and hyperglycaemic index, patients who reached their nutritional goals compared to those who did not, showed a hazard ratio (HR) of 0.199 for ICU mortality (CI 0.048-0.831; P = 0.027), a HR of 0.079 for 28 day mortality (CI 0.013-0.467; P = 0.005) and a HR of 0.328 for hospital mortality (CI 0.113-0.952; P = 0.04). Achievement of energy goals whilst not reaching protein goals, did not affect ICU mortality; the HR for 28 day mortality was 0.120 (CI 0.027-0.528; P = 0.005) and 0.318 for hospital mortality (CI 0.107-0.945; P = 0.039). No difference in outcome related to optimal feeding was found for men., Conclusions: Optimal nutritional therapy improves ICU, 28-day and hospital survival in female ICU patients. Female patients reaching both energy and protein goals have better outcomes than those reaching only the energy goal. In the present study men did not benefit from optimal nutrition.

The incidence of sepsis, the combination of a systemic inflammatory response syndrome and documented infection, is as high as up to 95 cases per 100,000 people per year. The understanding of the pathophysiology of sepsis has much increased over the last 20 years. However, sepsis combined with shock is still associated with a high mortality rate varying from 35 to 55%. Causative treatment, source control and antibiotics started as soon as possible, are the cornerstone of therapy in combination with symptomatic treatment in the ICU. The pharmacological interventions, including fluid resuscitation, vasoactive drugs and adjunctive drugs such as steroids, activated protein C are discussed. The possible beneficial role of strict glucose control is also addressed. Since many drug intervention studies were negative, lessons should be learned from earlier experiences for future trials. Source control and level of intensive care should be eliminated as confounders.

We present a 62-year-old man who over the years developed almost all the possible cardiac complications of radiation therapy after treatment of a Hodgkin's lymphoma. A review of the literature and a summary of treatment options for cardiac complications after irradiation of the mediastinum for Hodgkin's lymphoma are presented.

Background & Aims: When individual energy requirements of adult patients cannot be measured by indirect calorimetry, they have to be predicted with an equation. The aim of this study was to analyze which resting energy expenditure (REE) predictive equation was the best alternative to indirect calorimetry in adult patients., Methods: Predictive equations were included when based on weight, height, gender and/or age. REE was measured with indirect calorimetry. The mean squared prediction error was used to evaluate how well the equations fitted the REE measurement., Results: Eighteen predictive equations were included. Indirect calorimetry data were available for 48 outpatients and 45 inpatients. Also a subgroup of 42 underweight patients (BMI<18.5) was analyzed. The mean squared prediction error was 233-426 kcal/d and the percentage of patients with acceptable prediction was 28-52% for adult patients depending on the equation used. The FAO/WHO/UNU (1985) equation including both weight and height had the smallest prediction error in adult patients (233 kcal/d), outpatients (182 kcal/d), inpatients (277 kcal/d) as well as underweight patients (219 kcal/d)., Conclusions: The REE of adult outpatients, inpatients and underweight patients can best be estimated with the FAO/WHO/UNU equation including weight and height, when indirect calorimetry is not available.

Spontaneous remission of acute myeloid leukaemia (AML) is extremely rare and usually of short duration. We report two patients with documented AML who developed spontaneous remission of their leukaemia shortly after an episode of severe sepsis and respiratory failure requiring mechanical ventilation. The underlying mechanisms of spontaneous remission remain unclear but an association with preceding blood transfusions and severe systemic infections has been reported. An overwhelming immune response due to sepsis and leading to raised levels of TNF-alpha, INF-gamma, IL -2 and an increased activity of NK cells, cytotoxic T-cells and macrophages are thought to play an important role. Better insights into the mechanisms of spontaneous remission of AML after recovery from sepsis could help in developing new therapies for AML.

Psychotropic drugs can increase the risk of perioperative complications when given in combination with anaesthesia. Evidence-based guidelines that address this issue are lacking. Consensus-based recommendations were formed for the perioperative management of these patients based on the available literature and a systematic evaluation of perioperative risks by the medical specialists directly involved. Patients who use lithium, monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants or clozapine are at risk of experiencing adverse interactions. The anaesthesiology literature recommends discontinuing irreversible MAOIs and lithium in all cases, and tricyclic antidepressants in patients with systemic disorders. With the exception of lithium, the risks of psychiatric relapse or recurrence associated with discontinuation necessitate intensive integrated psychiatric treatment. Continuation of treatment under strict haemodynamic observation may also be an option in some cases. Patients taking selective serotonin reuptake inhibitors (SSRIs) should be observed carefully for psychological instability and physical abnormalities, and clinicians should be aware of medications that could increase the risk of haemorrhage when used in combination with SSRIs. In these cases, a psychiatrist should be consulted. The same is true for patients taking antipsychotic or other antidepressant medication who develop psychological instability or have a systemic disorder. Given the widespread use ofpsychotropic drugs and the seriousness of the associated risks, it is recommended that the decision whether to continue or discontinue psychotropic medication should become a standard component of preoperative assessment.

Different nutritional outcome studies on the same subject can have vast differences in composition of the chosen food without justification, suggesting that the composition of "optimal" nutrition in patients is not known or that optimal nutrition does not exist. The result will be negative studies which reinforces the existing impression that nutritional intervention is of limited value in every day's patient care. This perspective will put arguments forward that optimal nutrition exists and that the definition of optimal nutrition should be the base of future nutrition intervention studies. This perspective aims at providing a definition of optimal nutrition and consequently a basis to critically appraise the literature upon nutritional interventions in disease states.

In 7 women with premature labour pains, severe dyspnoea developed that was possibly related to the use of nifedipine as an 'off-label' tocolytic. 6 of these women had a twin pregnancy. Diuretics and oxygen therapy had little effect, but the patients recovered after the administration of nifedipine was stopped. The efficacy and safety of nifedipine as a tocolytic agent has been investigated in a number of well-designed randomised studies. However, these studies were performed in a selected group of pregnant women and women with multiple pregnancies or prematurely ruptured membranes were mostly excluded. It can be hypothesised that the respiratory complications in these cases are due to unequal ventilation/perfusion of the lungs in the presence of a physiologically elevated diaphragm due to the pregnancy. These changes are more pronounced in multiple pregnancies. After administration ofnifedipine, there is perfusion of atelectatic areas of the lung that are not or not well ventilated, resulting in ventilation-perfusion discrepancy and hence dyspnoea. Although case reports permit only limited extrapolation, these observations warrant caution with regard to the safety ofnifedipine as a tocolytic agent in patients with multiple pregnancies. The use of medication in groups of patients for which the agent has not been investigated, or which were explicitly excluded from the study, should be done with extreme caution. One should in any case be aware of the possible risks.

Introduction: Identification of risk factors for diminished cortisol response to adrenocorticotrophic hormone (ACTH) in the critically ill could facilitate recognition of relative adrenal insufficiency in these patients. Therefore, we studied predictors of a low cortisol response to ACTH., Methods: A retrospective cohort study was conducted in a general intensive care unit of a university hospital over a three year period. The study included 405 critically ill patients, who underwent a 250 microg ACTH stimulation test because of prolonged hypotension or need for vasopressor/inotropic therapy. Plasma cortisol was measured before and 30 and 60 min after ACTH injection. A low adrenal response was defined as an increase in cortisol of less than 250 nmol/l or a peak cortisol level below 500 nmol/l. Various clinical variables were collected at admission and on the test day., Results: A low ACTH response occurred in 63% of patients. Predictors, in multivariate analysis, included sepsis at admission, low platelets, low pH and bicarbonate, low albumin levels, high Sequential Organ Failure Assessment score and absence of prior cardiac surgery, and these predictors were independent of baseline cortisol and intubation with etomidate. Baseline cortisol/albumin ratios, as an index of free cortisol, were directly related and increases in cortisol/albumin were inversely related to disease severity indicators such as the Simplified Acute Physiology Score II and Sequential Organ Failure Assessment score (Spearman r = -0.21; P < 0.0001)., Conclusion: In critically ill patients, low pH/bicarbonate and platelet count, greater severity of disease and organ failure are predictors of a low adrenocortical response to ACTH, independent of baseline cortisol values and cortisol binding capacity in blood. These findings may help to delineate relative adrenal insufficiency and suggest that adrenocortical suppression occurs as a result of metabolic acidosis and coagulation disturbances.

In the management of critical care units, leadership and conflict management are vital areas for the successful performance of the unit. In this article a practical approach to define competencies for leadership and principles and practices of conflict management are offered. This article is, by lack of relevant intensive care unit (ICU) literature, not evidence based, but it is the result of personal experience and a study of literature on leadership as well on conflicts and negotiations in non-medical areas. From this, information was selected that was recognisable to the authors and, thus, also seems to be useful knowledge for medical doctors in the ICU environment.

Herpes simplex virus type 1 (HSV-1) has been associated with pulmonary disease, mostly in severely immunocompromised patients. After reactivation and shedding in the oropharynx, the virus may reach the lower respiratory tract by aspiration or by contiguous spread. HSV-1 can be detected in clinical specimens by virus culture or quantitatively by nucleic acid amplification techniques. With these techniques, HSV-1 is often detected in the respiratory secretions of critically-ill patients. However, a clear diagnosis of HSV-1 pneumonia is difficult to establish because clinical criteria, radiological features and laboratory findings all lack specificity. Lower respiratory tract HSV-1 infections have not been associated with specific risk-factors. There is also an absence of consistent data concerning the effect of antiviral treatment on the outcome of critically-ill patients. Further studies are needed to better define the pathogenic role of HSV-1 in the lower respiratory tract of these patients, to improve the diagnosis, and, especially, to assess the need for antiviral treatment in the individual patient.

We report the case of a 56-year-old postmenopausal woman who was referred to our Endocrinology Outpatient Clinic because of severe hyperhidrosis. She had a four-year history of excessive sweating of her face and upper body. On presentation no sweating could be documented. Physical examination was also unremarkable. It appeared that five days earlier her general practitioner had prescribed oxybutynin for urge incontinence and this accidentally cured her hyperhidrosis. She was diagnosed with idiopathic hyperhidrosis. We advised her to continue the oxybutynin and six months later, she was still symptom-free. Oral anticholinergic drugs are known to be effective for hyperhidrosis, but only anecdotal reports on oxybutynin can be found in the literature. Oxybutynin is not approved for hyperhidrosis, explaining the unfamiliarity with this medicine. This case shows that oxybutynin can be a very effective and simple treatment with only mild side effects. Therefore, oxybutynin merits consideration in patients with idiopathic hyperhidrosis. This report includes a concise review of the causes and treatment options of hyperhidrosis.

Background & Aims: Early enteral nutrition and tailored supply of nutrients have become standard in most of the intensive care units (ICU). So far little attention has been given to losses of energy in the stools. The purpose of this explorative study was to evaluate the energy losses of patients with loose stools, necessitating the use of a feces-collector device in a tertiary academic ICU., Methods: In a group of 13 fully enterally fed and mechanically ventilated patients with loose stools, the daily energy loss in feces was determined, using bomb calorimetry. Malabsorption was defined as an absorption capacity of 85% or less. Energy expenditure was determined with indirect calorimetry., Results: Six out of 13 (46%) patients fulfilled the criterion of malabsorption. The mean total energetic absorption capacity was 84.6+/-13.3%. The mean capacity of absorption of fat was 89.7+/-16.3%. The caloric value of energy loss had a mean of 301+/-259 kcal/day. Fecal fat loss proved not to be a good indicator of total fecal energy loss. A total of 4/13 patients (31%) had a net negative energy balance of over 500 kcal/day. A daily feces production of 250 g or more was a good predictor of malabsorption. Energy loss could accurately be predicted by using a factor 4.87 for the combined energetic value of protein and carbohydrates, if dry weight and fecal fat content are known., Conclusions: In this clinical study on ICU patients with loose stools, malabsorption proved to be a frequently occurring and so far unrecognized problem, contributing strongly to negative energy balances in 1/3 of the patients.

Context: Reducing aspiration of gastric contents by placing mechanically ventilated patients in a semirecumbent position has been associated with lower incidences of ventilator-associated pneumonia (VAP). The feasibility and efficacy of this intervention in a larger patient population, however, are unknown., Objective: Assessment of the feasibility of the semirecumbent position for intensive care unit patients and its influence on development of VAP., Design: In a prospective multicentered trial, critically ill patients undergoing mechanical ventilation were randomly assigned to the semirecumbent position, with a target backrest elevation of 45 degrees , or standard care (i.e., supine position) with a backrest elevation of 10 degrees ., Main Outcome Measures: Backrest elevation was measured continuously during the first week of ventilation with a monitor-linked device. A deviation of position was defined as a change of the randomized position >5 degrees . Diagnosis of VAP was made by quantitative cultures of samples obtained by bronchoscopic techniques., Results: One hundred nine patients were assigned to the supine group and 112 to the semirecumbent group. Baseline characteristics were comparable for both groups. Average elevations were 9.8 degrees and 16.1 degrees at day 1 and day 7, respectively, for the supine group and 28.1 degrees and 22.6 degrees at day 1 and day 7, respectively, for the semirecumbent group (p < .001). The target semirecumbent position of 45 degrees was not achieved for 85% of the study time, and these patients more frequently changed position than supine-positioned patients. VAP was diagnosed in eight patients (6.5%) in the supine group and in 13 (10.7%) in the semirecumbent group (NS), after a mean of 6 (range, 3-9) and 7 (range, 3-12) days, respectively. There were no differences in numbers of patients undergoing enteral feeding, receiving stress ulcer prophylaxis, or developing pressure sores or in mortality rates or duration of ventilation and intensive care unit stay between the groups., Conclusions: The targeted backrest elevation of 45 degrees for semirecumbent positioning was not reached in the conditions of the present randomized study. The achieved difference in treatment position (28 degrees vs. 10 degrees ) did not prevent the development of VAP.

A 57-year-old immunocompromized female developed a necrotizing fasciitis with sepsis a few days after abdominal complaints and diarrhoea. Surgery was performed because of progressive worsening of the patient's situation and during surgery the decision was made to perform an amputation. After surgery the patient was brought to the intensive care department for a few days. She recovered from her sepsis within a few days. Cultures showed Salmonella enteritidis.

Background: Fasting before surgery is still common care in a lot of western hospitals. Overnight fasting can induce postoperative insulin resistance. Insulin resistance has been shown to be related to infectious morbidity. It was shown that postoperative insulin resistance can be attenuated by preoperative intake of a clear carbohydrate-rich beverage. The aim of this study was to investigate whether preoperative intake of carbohydrate-rich beverages could postoperatively influence the immune system., Methods: In this randomized, controlled study, we investigated the effect of surgery on the postoperative immune response in 10 preoperatively fasted patients (control) and 2 groups of 10 patients receiving 2 different carbohydrate-rich beverages preoperatively, by measuring human leukocyte antigen (HLA)-DR expression on monocytes on the day before and on the day after surgery. Furthermore, we studied perioperative fluid homeostasis and preoperative well-being of the patients., Results: HLA-DR expression decreased significantly after surgery in the control group. Patients receiving any of the 2 carbohydrate-rich beverages did not show this postoperative decrease. Fluid homeostasis was not affected in any of the groups, and well-being tended to be better in patients receiving carbohydrate-rich beverages compared with controls., Conclusion: This study suggests that preoperative intake of a carbohydrate-rich beverage can prevent surgery-induced immunodepression and thus might reduce the risk of infectious complications.

Objectives: Poor survival of patients with a haematological malignancy admitted to the intensive care unit (ICU) prompts for proper admission triage and prediction of ICU treatment failure and long-term mortality. We therefore tried to find predictors of the latter outcomes., Methods: A retrospective analysis of charts and a prospective follow-up study were done, of haemato-oncological patients, admitted to our ICU in a 7-year period with a follow-up until 2 yr thereafter. Clinical parameters during the first four consecutive days were taken to calculate the simplified acute physiology (SAPS II) and the sequential organ failure assessment (SOFA) scores, of proven predictive value in general ICU populations., Results: From a total of 58 patients (n = 47 with acute myelogenous leukaemia or non-Hodgkin lymphoma), admitted into ICU mostly because of respiratory insufficiency, sepsis, shock or combinations, 36 patients had died during their stay in the ICU. Of ICU survivors (n = 22), 20 patients died during follow-up so that the 1-year survival rate was only 12%. The SAPS II and particularly the SOFA scores were of high predictive value for ICU and long-term mortality., Conclusions: Patients with life-threatening complications of haematological malignancy admitted to ICU ran a high risk for death in the ICU and on the long-term, and the risk can be well predicted by SOFA. The latter may help us to decide on intensive care in individual cases, in order to avoid potentially futile care for patients with a SOFA score of 15 or higher.

Patients with a long stay in the intensive care unit because of chronic critical illness consume many resources, and yet their outcome may be poor. We evaluated the long-term outcome of patients spending more than 60 days in the intensive care unit. We performed a retrospective cohort and prospective follow-up study of 78 patients staying more than 60 days in the 19-26 bed mixed intensive care unit of a university hospital from November 1995 to January 2003. The mortality in the intensive care unit was 38%; at 1 and 5 years it was 56% and 67%, respectively. Advanced age, prior pulmonary disease, long duration of renal replacement therapy, a low oxygenation ratio and platelet count and high Simplified Acute Physiology Score II and Sequential Organ Failure Assessment scores on day 60 influenced long-term mortality. A Simplified Acute Physiology Score II of 50 or a Sequential Organ Failure Assessment score of 8 or higher was associated with 100% mortality during follow-up. The overall 5-year survival rate of 33% suggests that prolonged intensive care may be worth the effort in certain patients.

Sarcoidosis is a multisystem granulomatous disorder characterised pathologically by the presence of noncaseating granulomas in the organs involved. Cardiac involvement, although well known, is rare. We describe a 72-year-old patient who was admitted to the intensive care unit after coronary artery bypass grafting. She developed refractory right and left ventricular failure complicated by multiple organ failure and died three days later. Postmortem examination revealed extensive sarcoidosis. On hindsight, preoperative ventricular tachycardia and an abnormal perfusion-ventilation scintigraphy of the lungs were manifestations of an underlying sarcoidosis.

Background: The objective is to study the population pharmacokinetics of lorazepam and midazolam in critically ill patients with acute renal failure who are treated with continuous venovenous hemofiltration (CVVH)., Methods: Twenty critically ill patients with acute renal failure on CVVH therapy were administered either lorazepam (n = 10) or midazolam (n = 10) by continuous infusion. CVVH was performed with an ultrafiltrate flow of 2 L/h with filtrate substitution in the predilution or postdilution mode. Blood flow through the 1.9-m 2 cellulose triacetate membrane filter was 180 mL/min. For 48 hours, multiple blood and ultrafiltrate samples were obtained for determination of concentrations of the drug and its metabolites., Results: The pharmacokinetics of lorazepam is described best by a 1-compartment model. No significant covariates were identified. Total-body clearance was 6.4 L/h, and volume of distribution was 376 L. Ultrafiltration clearance was 0.31 L/h, equivalent to approximately 5% of total clearance. Average degree of plasma protein binding was 82.9% for lorazepam, with a sieving coefficient of 0.16 +/- 0.03. For lorazepamglucuronide, degree of plasma protein binding was 39.5%, and sieving coefficient was 0.48 +/- 0.07. The pharmacokinetics of midazolam is described best by a 1-compartment model. No significant covariates were identified. Total-body clearance was 8.5 L/h, and volume of distribution was 157 L. Clearance by ultrafiltration was 0.055 L/h, equivalent to approximately 0.7% of total clearance. Average degree of plasma protein binding was 95.8%, with a sieving coefficient of 0.04 +/- 0.03. For the metabolite 1-hydroxymidazolamglucuronide, average degree of plasma protein binding was 43.4%, with a sieving coefficient of 0.45 +/- 0.06., Conclusion: Neither lorazepam nor midazolam is removed efficiently by CVVH. CVVH contributes significantly to the removal of the glucuronide metabolites lorazepamglucuronide and 1-hydroxymidazolamglucuronide.

Introduction: The pathogenicity of late respiratory infections with herpes simplex virus type 1 (HSV-1) in the critically ill is unclear., Methods: In four critically ill patients with persistent pulmonary infiltrates of unknown origin and isolation of HSV-1 from tracheal aspirate or bronchoalveolar lavage fluid, at 7 (1-11) days after start of mechanical ventilatory support, a pulmonary leak index (PLI) for 67Gallium (67Ga)-transferrin (upper limit of normal 14.1 x 10(-3)/min) was measured., Results: The PLI ranged between 7.5 and 14.0 x 10(-3)/min in the study patients. Two patients received a course of acyclovir and all survived., Conclusions: The normal capillary permeability observed in the lungs argues against pathogenicity of HSV-1 in the critically ill, and favors that isolation of the virus reflects reactivation in the course of serious illness and immunodepresssion, rather than primary or superimposed infection in the lungs.

Background: The clinical significance and pulmonary pathogenicity of herpes simplex virus type 1 (HSV-1) in mechanically ventilated, critically ill patients are unclear., Objective: To determine the clinical features and course of respiratory HSV-1 infections/colonisations in the critically ill, in order to evaluate the contribution to outcome., Design: A retrospective cohort study in the intensive care unit of an university hospital, involving 22 patients with a HSV-1 isolated from bronchoalveolar lavage (BAL) fluid, divided into survivors (n = 13) and non-survivors (n = 9). All patients except for one survivor had been intubated and were mechanically ventilated., Results: Non-survivors had acquired HSV-1 sooner on mechanical ventilation than survivors. Prior chronic heart disease was more prevalent in non-survivors than in survivors and, at the time of HSV-1 isolation, the mean creatinine level was higher (P < 0.05) in the former. Survivors had a somewhat greater fall in body temperature after a 10-day course of antiviral therapy than non-survivors, but the lung radiographic abnormalities prior to and after the course did not differ. There were no major differences in cardiorespiratory variables between outcome groups and causes of death and were judged not to relate, in general, to HSV-1., Conclusions: Critically ill patients in whom HSV-1 from BAL is isolated, have about 40% chance of dying, mainly because of severe underlying disease and comorbidity, which may predispose to endogenous reactivation of the virus. There is no clinical evidence for direct cardiorespiratory pathogenicity and beneficial effects of antiviral therapy. HSV-1 isolated from lung secretions may thus be a marker rather than a mediator of severe illness.

We describe a 61-year-old patient who had been suffering from chronic ulcers of both legs for 18 months. Initially, his condition was diagnosed as ischaemic because of an ankle-brachial index of 0.6, as confirmed by additional angiography. A successful femoro-infragenual bypass procedure was performed, but the ulcers increased in size and number. He was then extensively analysed for a possible (macro)vascular origin of his symptoms. Angiographic analysis of both legs showed no arterial stenosis or occlusion. Despite the extensive experience of the vascular surgeons with leg ulcers, consultations by internal medicine, vascular medicine and dermatology, and tissue examination by our pathologists, pyoderma gangrenosum was not recognised. During a multidisciplinary meeting one of the specialists, to whom the lesions were shown, immediately considered the diagnosis on clinical grounds. The additional finding of IgG-kappa paraproteinaemia and improvement of the ulcers on treatment with corticosteroids were consistent with the diagnosis. Although the majority of patients on the vascular surgery ward have ulcers caused by ischaemia or a combined arterial/venous origin, another (rare) cause, namely pyoderma gangrenosum in association with IgG-kappa paraproteinaemia without the presence of multiple myeloma, should be taken into account.

In a 75-year-old man who had experienced a serious nosebleed, as a consequence of collapsing, the nose was packed bilaterally. An evaluation of the dyspnoeic complaints revealed abnormal blood gas values which indicated hypoxemia. Ventilation perfusion scintigraphy and a lung function test did not reveal any abnormalities. Prior to additional investigations, the packing was removed and then the complaints disappeared and the blood gas values returned to normal. That nose packing can lead to arterial hypoxemia, with or without hypercapnia, has already been described. The underlying mechanism is probably determined multifactorially and is not completely clear. Control of the oxygen saturation seems to be indicated for patients with packing, and nasal obstruction should be considered in the differential diagnosis of hypoxemia.

Phaeochromocytomas are rare neuroendocrine tumours that produce symptoms through excess release of catecholamines. Treatment of choice is elective, complete surgical removal after pretreatment with alpha-adrenergic blocking drugs, to prevent dangerous haemodynamic fluctuations. In rare cases a 'catecholamine crisis' develops presenting with pulmonary oedema and circulatory shock. We report such a case of a patient with familial extra-adrenal phaeochromocytoma who successfully underwent emergency surgery. Pathophysiological mechanisms are discussed. Although pretreatment with alpha-adrenergic blocking drugs seems advisable in terms of morbidity and mortality, the concept is based on theory rather than clinical evidence. Surgical management of a catecholamine crisis is associated with high mortality rates. However, proof of better outcome by avoidance or discontinuation of emergency surgery is not available. Based on literature and on this case, we conclude that emergency surgery in phaeochromocytoma does not have to be structurally avoided and may be considered under life-threatening circumstances.

Two cases are presented of intentional intoxications with the tricyclic antidepressants (TCAs) nortriptyline (NT) and amitriptyline (AT). The peak plasma concentrations were 2290 microg/L and 2900 microg/L, respectively. The active metabolites E-10-hydroxynortriptyline (EHNT) and Z-10-hydroxynortriptyline (ZHNT) profiles were quite different as monitored for 5 to 10 days after presumed drug intake. In conclusion, these cases illustrate that (1) metabolite formation and elimination after intake of an overdose dose of NT and AT are stereoselective, and (2) NT and EHNT toxicokinetics and toxicodynamics are quite different. It also shows that a patient with a severe TCA overdose can still survive if he or she receives appropriate and quick supportive care, even if the prognostic markers QRS time, coma grade, and serum TCA levels predict poor outcome.

Cervical necrotizing fasciitis (CNF) with thoracic extension is rare. It has never been reported in laryngectomized patients. A case of fatal CNF in a laryngectomized patient equipped with a voice prosthesis is presented. Diagnosis and treatment are discussed. CNF with thoracic extension was diagnosed on clinical picture, computed tomography (CT) and biopsies were taken just above the tracheostoma. Antibiotic treatment was started and extensive debridement of the affected tissues performed. A minor extension to the left pleura was considered irresectable. Irradical debridement and the impossibility of administering hyperbaric oxygen therapy caused death within two day after presentation. CNF is a rare disease and to our knowledge, has never been reported after total laryngectomy. This case emphasizes the need for early antibiotic treatment and radical surgical resection of the affected tissues.

Invasive aspergillosis is a well-known complication in immunocompromised patients. There are only a few reports of invasive aspergillosis in non-immunocompromised patients. We describe a 72-year-old female patient with clinical signs of spondylodiskitis occurring 4 months after what had appeared to be successful treatment of pulmonary aspergillosis. The patient used inhalation corticosteroids on a daily basis because of chronic obstructive pulmonary disease (COPD). Spondylodiskitis of the intervertebral disc Th11 and Th12 with involvement of both adjacent vertebral bodies was confirmed by magnetic resonance imaging. Histopathological examination revealed the presence of septate hyphae, indicative of Aspergillus species. Subsequently, evidence of Aspergillus spondylodiskitis was obtained by amplification of Aspergillus-DNA with a specific polymerase chain reaction method. Aspergillus spondylodiskitis after pulmonary aspergillosis is only very rarely encountered. Patients with COPD, managed with short-term courses of systemic corticosteroids or with high-dose corticosteroid inhalation therapies, are considered non-immunocompromised but might be at risk of developing invasive aspergillosis.

Because sinusitis is usually clinically silent in intubated patients, it is not widely appreciated as an important source of infection and fever in critically ill patients. Three such patients, two men aged 22 and 36 years, and a woman aged 50 years, suffered from respiratory insufficiency due to pneumonia. The course of the disease was determined by the sinusitis, which did not resolve during antibiotic therapy of the pneumonia, notwithstanding the fact that the causative micro-organism was susceptible to the antibiotics administered, and that both the tracheal and gastric tubes were led through the mouth instead of the nose. Flushing of the sinuses caused the fever to disappear and led to recovery of the patients. An aggressive approach to diagnose sinusitis in the intubated patient with fever in the intensive care unit is needed. A maxillary sinus lavage and culture, followed by treatment with specific antibiotics should be an integral part of the diagnosis and treatment in these patients. Surgery is indicated in the event of persistent sepsis.

A case of Chlamydia pneumoniae infection with bilateral pleural effusion and a subsegmental pulmonary infiltrate in an intubated and mechanically ventilated critically ill patient is described. Diagnosis was made by polymerase chain reaction on both pleural effusions.

A man aged 73, admitted because of unstable angina pectoris also had a anaemia with a haemoglobin concentration of 2.8 mmol/l. The department of Consultative Internal Medicine was asked to elucidate this anaemia. The anamnesis proved to contain extensive diagnostic tests concerning the anaemia which had had no results. In spite of a negative anamnesis, the low serum iron level had prompted an unsuccessful search for a source of haemorrhage in the proximal and distal parts of the digestive tract. The bone marrow had been examined three times without a clear diagnosis. It was also found that there had been a deviation from the classification of anaemia which should be guided by the size of the erythrocyte and the reticulocyte count. This had resulted in diagnostics that where inconvenient to the patient; also the patient had been treated without success with ferrofumarate. Ultimately, he proved to suffer from autoimmune hypothyroidism; the anaemia was resolved by substitution therapy.

Acute Physiology and Chronic Health Evaluation (APACHE) II scoring is widely used as an index of illness severity, for outcome prediction, in research protocols and to assess intensive care unit performance and quality of care. Despite its widespread use, little is known about the reliability and validity of APACHE II scores generated in everyday clinical practice. We retrospectively re-assessed APACHE II scores from the charts of 186 randomly selected patients admitted to our medical and surgical intensive care units. These 'new' scores were compared with the original scores calculated by the attending physician. We found that most scores calculated retrospectively were lower than the original scores; 51% of our patients would have received a lower score, 26% a higher score and only 23% would have remained unchanged. Overall, the original scores changed by an average of 6.4 points. We identified various sources of error and concluded that wide variability exists in APACHE II scoring in everyday clinical practice, with the score being generally overestimated. Accurate use of the APACHE II scoring system requires adherence to strict guidelines and regular training of medical staff using the system.

Objective: To assess the value of alpha-atrial natriuretic peptide (alpha-ANP), second messenger cyclic guanosine monophosphate (cGMP,) and endothelin as markers of myocardial depression in septic shock., Design: Prospective observational study., Setting: Medical intensive care unit (ICU) of a university hospital., Patients: Fourteen consecutive patients with septic shock and arterial and pulmonary artery catheters in place., Measurements and Main Results: Hemodynamic variables and plasma levels of alpha-ANP, cGMP, and endothelin were measured every 6 hrs for 3 days after admission. Eight patients died from shock in the ICU. The nadir left ventricular stroke work index (LVSWI) was below 35 g/m2 in all patients, and the median peak circulating alpha-ANP (n < 68 pg/mL) was 276 pg/mL (range, 79-1056), the median peak cGMP (n < 2.1 ng/mL) was 8.1 ng/mL (range, 3.2-29.7), and the median peak endothelin (n < 5.3 pg/mL) was 15.5 pg/mL (range, 8.5-33.9), supranormal in all patients. Outcome groups differed in the course of cardiac index and LVSWI, which were lower in nonsurvivors despite similar filling pressures and more intensive inotropic treatment (p < .01). The course of alpha-ANP, cGMP, and endothelin plasma levels also differed between groups, with higher levels in nonsurvivors (p < .05). As for pooled data, the mean daily or nadir LVSWI inversely related to mean daily or peak alpha-ANP, cGMP, and endothelin levels, respectively (p < .05). The area under the receiver operating characteristic curve for myocardial depression (LVSWI < 35 g/m2) was for alpha-ANP and endothelin 0.77, and for cGMP 0.85 (p < .01). The optimum cutoff values for alpha-ANP, cGMP, and endothelin were 172 pg/mL, 4.5 ng/mL, and 10.0 pg/mL, respectively. The sensitivity for myocardial depression of alpha-ANP, cGMP, and endothelin was 68%, 77%, and 72%, and the specificity was 82%, 93%, and 69%, respectively., Conclusions: Circulating alpha-ANP, endothelin, and, particularly, cGMP may be markers of the myocardial depression of human septic shock, which is associated with mortality.

In the early years of intensive care a stress ulcer related bleeding, occurring in 20-30% of the IC population, became recognized as a significant cause of morbidity and mortality. Due to improved intensive care medicine (including adequate early resuscitation, analgesia, sedation) the incidence of stress ulcer-related bleeding in the IC has decreased markedly. Without pharmacological prophylaxis incidences ranging from 0.6 to 6% were reported. It is not recommended to apply stress ulcer prophylaxis on a routine basis, it should be reserved for patients with an increased risk of a stress ulcer-related bleeding. In patients with neurotrauma, severe burn, recent peptic ulcer or bleeding and those with coagulopathy prophylaxis with ranitidine is advised.

Objective: To evaluate the effectiveness of lorazepam and midazolam for long-term sedation of critically ill, mechanically ventilated patients., Design: Double-blind, randomized, controlled study., Setting: Medical intensive care unit in a university teaching hospital., Patients: Sixty-four evaluable adult patients admitted to the intensive care department requiring mechanical ventilation for >3 days., Interventions: Patients were randomized to receive blinded solutions of either lorazepam or midazolam by continuous infusion. The lowest dose that achieved an adequate sedation was infused. The maximum dose allowed for each drug was 60 mg/hr for midazolam and 4 mg/hr for lorazepam. Sedation was assessed initially and at least every 8 hrs thereafter on a seven-point scale if the sedation was adequate and every 2 hrs if it was not., Measurements and Main Results: Measurements included the score on the sedation scale, the time between determination of the desired level of sedation and the achievement of that level, and plasma concentrations. It is significantly easier to reach a desired level of sedation with lorazepam than with midazolam. No difference in recovery was found in the 24 hrs after discontinuation of therapy. The fact that there are many factors influencing midazolam pharmacokinetics may explain the more difficult management of desired sedation levels. The equipotent dose of 10 mg of midazolam proved to be 0.7 mg of lorazepam in long-term sedation. The average cost for therapy with midazolam was approximately ten times more than that with lorazepam., Conclusions: Lorazepam is a useful alternative to midazolam for the long-term sedation of patients in the medical intensive care unit and provides easier management of the sedation level. Sedation with lorazepam offers a significant cost-savings.

Unlabelled: Parenteral nutrition is associated with liver enzyme abnormalities. Until 1993 the incidence of icterus was low in both academic hospitals in Amsterdam, the Netherlands (Academic Medical Centre (AMC) and Academic Hospital of the Free University (AZVU)). In 1993 Intralipid in the nutrition was replaced by Endolipid in the home total parenteral nutrition programme (AMC) and by Lipofundin S in AZVU. Fifty per cent of the patients in the home programme developed severe fatigue, jaundice and thrombocytopenia. These signs and symptoms disappeared over months when parenteral nutrition without fat was given. After reintroduction of Intralipid these signs and symptoms never recurred. In AZVU the incidence of jaundice increased from 21% in 1992 to 79% in 1993 (p = 0.0002). After reintroduction of Intralipid in 1994 the incidence of jaundice decreased to 16%., Conclusion: Although the lipid emulsions are equivalent according to the product specification, the described observation suggests that Lipofundin S and Endolipid cause more icterus than Intralipid, possibly caused bij an impurity in the fat emulsion.