Hans Pargger

Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: a randomised study

In patients with ventilator-associated pneumonia (VAP), guidelines recommend antibiotic therapy adjustment according to microbiology results after 72 h. Circulating procalcitonin levels may provide evidence that facilitates the reduction of antibiotic therapy. In a multicentre, randomised, controlled trial, 101 patients with VAP were assigned to an antibiotic discontinuation strategy according to guidelines (control group) or to serum procalcitonin concentrations (procalcitonin group) with an antibiotic regimen selected by the treating physician. The primary end-point was antibiotic-free days alive assessed 28 days after VAP onset and analysed on an intent-to-treat basis. Procalcitonin determination significantly increased the number of antibiotic free-days alive 28 days after VAP onset (13 (2–21) days versus 9.5 (1.5–17) days). This translated into a reduction in the overall duration of antibiotic therapy of 27% in the procalcitonin group (p = 0.038). After adjustment for age, microbiology and centre effect, the rate of antibiotic discontinuation on day 28 remained higher in the procalcitonin group compared with patients treated according to guidelines (hazard rate 1.6, 95% CI 1.02–2.71). The number of mechanical ventilation-free days alive, intensive care unit-free days alive, length of hospital stay and mortality rate on day 28 for the two groups were similar. Serum procalcitonin reduces antibiotic therapy exposure in patients with ventilator associated pneumonia.

Rivastigmine for the prevention of postoperative delirium in elderly patients undergoing elective cardiac surgery : A randomized controlled trial

Objective:Cardiac surgery is frequently followed by postoperative delirium, which is associated with increased 1-year mortality, late cognitive deficits, and higher costs. Currently, there are no recommendations for pharmacologic prevention of postoperative delirium. Impaired cholinergic transmission is believed to play an important role in the development of delirium. We tested the hypothesis that prophylactic short-term administration of oral rivastigmine, a cholinesterase inhibitor, reduces the incidence of delirium in elderly patients during the first 6 days after elective cardiac surgery. Design:Double-blind, randomized, placebo-controlled trial. Setting:One Swiss University Hospital. Patients:One hundred twenty patients aged 65 or older undergoing elective cardiac surgery with cardiopulmonary bypass. Intervention:Patients were randomly assigned to receive either placebo or 3 doses of 1.5 mg of oral rivastigmine per day starting the evening before surgery and continuing until the evening of the sixth postoperative day. Measurements and Main Results:The primary predefined outcome was delirium diagnosed with the Confusion Assessment Method within 6 days postoperatively. Secondary outcome measures were the results of daily Mini-Mental State Examinations and clock drawing tests, and the use of a rescue treatment consisting of haloperidol and/or lorazepam in patients with delirium. Delirium developed in 17 of 57 (30%) and 18 of 56 (32%) patients in the placebo and rivastigmine groups, respectively (p = 0.8). There was no treatment effect on the time course of Mini-Mental State Examinations and clock drawing tests (p = 0.4 and p = 0.8, respectively). There was no significant difference in the number of patients receiving haloperidol (18 of 57 and 17 of 56, p = 0.9) or lorazepam (38 of 57 and 35 of 56, p = 0.6) in the placebo and rivastigmine groups, respectively. Conclusion:This negative or, because of methodologic issues, possibly failed trial does not support short-term prophylactic administration of oral rivastigmine to prevent postoperative delirium in elderly patients undergoing elective cardiac surgery with cardiopulmonary bypass.

Cerebral perfusion in sepsis-associated delirium.

IntroductionThe pathophysiology of sepsis-associated delirium is not completely understood and the data on cerebral perfusion in sepsis are conflicting. We tested the hypothesis that cerebral perfusion and selected serum markers of inflammation and delirium differ in septic patients with and without sepsis-associated delirium.MethodsWe investigated 23 adult patients with sepsis, severe sepsis, or septic shock with an extracranial focus of infection and no history of intracranial pathology. Patients were investigated after stabilisation within 48 hours after admission to the intensive care unit. Sepsis-associated delirium was diagnosed using the confusion assessment method for the intensive care unit. Mean arterial pressure (MAP), blood flow velocity (FV) in the middle cerebral artery using transcranial Doppler, and cerebral tissue oxygenation using near-infrared spectroscopy were monitored for 1 hour. An index of cerebrovascular autoregulation was calculated from MAP and FV data. C-reactive protein (CRP), interleukin-6 (IL-6), S-100β, and cortisol were measured during each data acquisition.ResultsData from 16 patients, of whom 12 had sepsis-associated delirium, were analysed. There were no significant correlations or associations between MAP, cerebral blood FV, or tissue oxygenation and sepsis-associated delirium. However, we found a significant association between sepsis-associated delirium and disturbed autoregulation (P = 0.015). IL-6 did not differ between patients with and without sepsis-associated delirium, but we found a significant association between elevated CRP (P = 0.008), S-100β (P = 0.029), and cortisol (P = 0.011) and sepsis-associated delirium. Elevated CRP was significantly correlated with disturbed autoregulation (Spearman rho = 0.62, P = 0.010).ConclusionIn this small group of patients, cerebral perfusion assessed with transcranial Doppler and near-infrared spectroscopy did not differ between patients with and without sepsis-associated delirium. However, the state of autoregulation differed between the two groups. This may be due to inflammation impeding cerebrovascular endothelial function. Further investigations defining the role of S-100β and cortisol in the diagnosis of sepsis-associated delirium are warranted.Trial registrationClinicalTrials.gov NCT00410111.

Interleukin-6 and acute-phase protein concentrations in surgical intensive care unit patients: diagnostic signs in nosocomial infection.

ObjectiveTo determine the value of serum concentrations of interleukin-6 (IL-6), C-reactive protein, and glycosylation of α-acid glycoprotein as tools for diagnosing nosocomial infection in surgical intensive care unit (ICU) patients. DesignProspective, consecutive entry study of patients with an anticipated stay of at least 24 hrs in a surgical ICU. SettingUniversity hospital, a major provider of acute surgical care. PatientsOne hundred four consecutive patients admitted to the surgical ICU between March and June 1990. MeasurementsConcentrations of IL-6, C-reactive protein, and glycosylation of α1-acid glycoprotein were measured on days 1 and 6 after ICU admission. Clinical evaluation for infection was performed daily in a blinded fashion, i.e., without knowing the results of the acute-phase parameters. Main ResultsOn day 6 after surgery or trauma, nosocomial infection could be ascertained in 13 cases. The clinical parameter-of fever >38°C had a sensitivity of 54% and a specificity of 90% to demonstrate nosocomial infection. Infected patients showed increased concentrations of IL-6 (p < .001), C-reactive protein (p < .001), and increased reactivity of α1-acid glycoprotein to concanavalin A (p < .001) compared with patients without infections. By choosing appropriate cutoff values, IL-6 determinations had the highest specificity (97%), and C-reactive protein values had the highest sensitivity (85%) for diagnosing nosocomial infections. In uninfected patients, 81% of the IL-6 values, but only 29% of the C-reactive protein values, were back to the normal range on day 6 after injury. ConclusionDue to the rapid normalization after trauma, a single measurement of the serum IL-6 concentration may be useful to support or refute the clinical suspicion of nosocomial infection. (Crit Care Med 1993; 21:1175–1180)

Gastric intramucosal pH-guided therapy in patients after elective repair of infrarenal abdominal aneurysms: is it beneficial?

ObjectiveTo determine if gastric intramucosal pH (pHi)-guided therapy reduces the number of complications and length of stay in the intensive care unit (ICU) or the hospital after elective repair of infrarenal abdominal aortic aneurysms.DesignProspective, randomized study.SettingSurgical intensive care unit (SICU) of a University Hospital.PatientsFifty-five consecutive patients randomized to group 1 (pHi-guided therapy) or to group 2 (control).InterventionsPatients of group 1 with a pHi of lower than 7.32 were treated by means of a prospective protocol in order to increase their pHi to 7.32 or more.Measurements and resultspHi was determined in both groups on admission to the SICU and thereafter at 6-h intervals. In group 2, the treating physicians were blinded for the pHi values. Complications, APACHE II scores, duration of endotracheal intubation, fluid and vasoactive drug treatment, treatment with vasoactive drugs, length of stay in the SICU and in the hospital and hospital mortality were recorded. There were no differences between groups in terms of the incidence of complications. We found no differences in APACHE II scores on admission, the duration of intubation, SICU or hospital stay, or hospital mortality. In the two groups the incidence of pHi values lower than 7.32 on admission to the SICU was comparable (41 % and 42 % in groups 1 and 2, respectively). Patients with pHi lower than 7.32 had more major complications during SICU stay (p<0.05), and periods more than 10 h of persistently low pHi values (< 7.32) were associated with a higher incidence of SICU complications (p<0.01).ConclusionsLow pHi values (<7.32) and their persistence are predictors of major complications. Treatment to elevate low pHi values does not improve postoperative outcome. Based on these data, we cannot recommend the routine use of gastric tonometers for pHi-guided therapy in these patients. Further studies are warranted to determine adequate treatment of low pHi values that results in beneficial effects on the patient’s postoperative course and outcome.

Succinylcholine versus rocuronium for rapid sequence intubation in intensive care: a prospective, randomized controlled trial

IntroductionSuccinylcholine and rocuronium are widely used to facilitate rapid sequence induction (RSI) intubation in intensive care. Concerns relate to the side effects of succinylcholine and to slower onset and inferior intubation conditions associated with rocuronium. So far, succinylcholine and rocuronium have not been compared in an adequately powered randomized trial in intensive care. Accordingly, the aim of the present study was to compare the incidence of hypoxemia after rocuronium or succinylcholine in critically ill patients requiring an emergent RSI.MethodsThis was a prospective randomized controlled single-blind trial conducted from 2006 to 2010 at the University Hospital of Basel. Participants were 401 critically ill patients requiring emergent RSI. Patients were randomized to receive 1 mg/kg succinylcholine or 0.6 mg/kg rocuronium for neuromuscular blockade. The primary outcome was the incidence of oxygen desaturations defined as a decrease in oxygen saturation ≥ 5%, assessed by continuous pulse oxymetry, at any time between the start of the induction sequence and two minutes after the completion of the intubation. A severe oxygen desaturation was defined as a decrease in oxygen saturation ≥ 5% leading to a saturation value of ≤ 80%.ResultsThere was no difference between succinylcholine and rocuronium regarding oxygen desaturations (succinylcholine 73/196; rocuronium 66/195; P = 0.67); severe oxygen desaturations (succinylcholine 20/196; rocuronium 20/195; P = 1.0); and extent of oxygen desaturations (succinylcholine -14 ± 12%; rocuronium -16 ± 13%; P = 0.77). The duration of the intubation sequence was shorter after succinycholine than after rocuronium (81 ± 38 sec versus 95 ± 48 sec; P = 0.002). Intubation conditions (succinylcholine 8.3 ± 0.8; rocuronium 8.2 ± 0.9; P = 0.7) and failed first intubation attempts (succinylcholine 32/200; rocuronium 36/201; P = 1.0) did not differ between the groups.ConclusionsIn critically ill patients undergoing emergent RSI, incidence and severity of oxygen desaturations, the quality of intubation conditions, and incidence of failed intubation attempts did not differ between succinylcholine and rocuronium.Trial RegistrationClinicalTrials.gov, number NCT00355368.

Hand hygiene in the intensive care unit

Healthcare-associated infections affect 1.4 million patients at any time worldwide, as estimated by the World Health Organization. In intensive care units, the burden of healthcare-associated infections is greatly increased, causing additional morbidity and mortality. Multidrug-resistant pathogens are commonly involved in such infections and render effective treatment challenging. Proper hand hygiene is the single most important, simplest, and least expensive means of preventing healthcare-associated infections. In addition, it is equally important to stop transmission of multidrug-resistant pathogens. According to the Centers for Disease Control and Prevention and World Health Organization guidelines on hand hygiene in health care, alcohol-based handrub should be used as the preferred means for routine hand antisepsis. Alcohols have excellent in vitro activity against Gram-positive and Gram-negative bacteria, including multidrug-resistant pathogens, such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci, Mycobacterium tuberculosis, a variety of fungi, and most viruses. Some pathogens, however, such as Clostridium difficile, Bacillus anthracis, and noroviruses, may require special hand hygiene measures. Failure to provide user friendliness of hand hygiene equipment and shortage of staff are predictors for noncompliance, especially in the intensive care unit setting. Therefore, practical approaches to promote hand hygiene in the intensive care unit include provision of a minimal number of handrub dispensers per bed, monitoring of compliance, and choice of the most attractive product. Lack of knowledge of guidelines for hand hygiene, lack of recognition of hand hygiene opportunities during patient care, and lack of awareness of the risk of cross-transmission of pathogens are barriers to good hand hygiene practices. Multidisciplinary programs to promote increased use of alcoholic handrub lead to an increased compliance of healthcare workers with the recommended hand hygiene practices and a reduced prevalence of nosocomial infections.

Pancreatic stone protein : a marker of organ failure and outcome in ventilator-associated pneumonia

BACKGROUND Ventilator-associated pneumonia (VAP) is the most common hospital-acquired, life-threatening infection. Poor outcome and health-care costs of nosocomial pneumonia remain a global burden. Currently, physicians rely on their experience to discriminate patients with good and poor outcome. However, standardized prognostic measures might guide medical decisions in the future. Pancreatic stone protein (PSP)/regenerating protein (reg) is associated with inflammation, infection, and other disease-related stimuli. The prognostic value of PSP/reg among critically ill patients is unknown. The aim of this pilot study was to evaluate PSP/reg in VAP. METHODS One hundred one patients with clinically diagnosed VAP were assessed. PSP/reg was retrospectively analyzed using deep-frozen serum samples from VAP onset up to day 7. The main end point was death within 28 days after VAP onset. RESULTS Serum PSP/reg was associated with the sequential organ failure assessment score from VAP onset (Spearman rank correlation coefficient 0.49 P < .001) up to day 7. PSP/reg levels at VAP onset were elevated in nonsurvivors (n = 20) as compared with survivors (117.0 ng/mL [36.1-295.3] vs 36.3 ng/mL [21.0-124.0] P = .011). The areas under the receiver operating characteristic curves of PSP/reg to predict mortality/survival were 0.69 at VAP onset and 0.76 at day 7. Two PSP/reg cutoffs potentially allow for identification of individuals with a particularly good and poor outcome. Whereas PSP/reg levels below 24 ng/mL at VAP onset were associated with a good chance of survival, levels above 177 ng/mL at day 7 were present in patients with a very poor outcome. CONCLUSIONS Serum PSP/reg is a biomarker related to organ failure and outcome in patients with VAP. TRIAL REGISTRY ISRCTN.org; No.: ISRCTN61015974; URL: www.isrctn.org.

Occlusive mesenteric ischemia and its effects on jejunal intramucosal pH, mesenteric oxygen consumption and oxygen tensions from surfaces of the jejunum in anesthetized pigs

AbstractObjective: To investigate the effects of superior mesenteric artery (SMA) flow reduction on the jejunal intramucosal pH (pHi) and to compare these effects with corresponding changes of mesenteric oxygen transport variables and oxygen tensions on the surfaces of the jejunal serosa and mucosa. Design: Prospective, randomized, controlled, experimental study. Setting: Animal research laboratory. Subjects: 20 domestic pigs. Interventions: Mechanical flow reduction in the SMA. The animals were randomized to have an SMA flow of 0%, 25%, 38%, 50% or 100% (control). Measurements and main results: Measurements (baseline, ischemia, reperfusion) consisted of hemodynamic and oxygen transport variables, SMA blood flow, mesenteric oxygen transport variables, pHi and oxygen tensions of the jejunal serosa and mucosa. Flow reduction in the SMA resulted in a significant decrease of pHi indicating ischemia earlier than mesenteric oxygen transport variables. The relationship between mesenteric oxygen delivery (DO2ms) and pHi during acute ischemia is best described by a sigmoid curve. There was a linear correlation between the changes of the jejunal surface oxygen tensions and pHi due to SMA flow reduction. Conclusion: The sigmoid relationship between pHi and DO2ms indicated that pHi is a sensitive parameter for detecting ischemia at 50% of the baseline oxygen delivery and that below 25% there was no further decrease of pHi. In contrast, mesenteric and whole body oxygen transport parameters were not indicative of impaired mucosal oxygen supply.

Midregional pro-atrial natriuretic peptide and procalcitonin improve survival prediction in VAP

Ventilator-associated pneumonia (VAP) affects mortality, morbidity and cost of critical care. Reliable risk estimation might improve end-of-life decisions, resource allocation and outcome. Several scoring systems for survival prediction have been established and optimised over the last decades. Recently, new biomarkers have gained interest in the prognostic field. We assessed whether midregional pro-atrial natriuretic peptide (MR-proANP) and procalcitonin (PCT) improve the predictive value of the Simplified Acute Physiologic Score (SAPS) II and Sequential Related Organ Failure Assessment (SOFA) in VAP. Specified end-points of a prospective multinational trial including 101 patients with VAP were analysed. Death <28 days after VAP onset was the primary end-point. MR-proANP and PCT were elevated at the onset of VAP in nonsurvivors compared with survivors (p = 0.003 and p = 0.017, respectively) and their slope of decline differed significantly (p = 0.018 and p = 0.039, respectively). Patients with the highest MR-proANP quartile at VAP onset were at increased risk for death (log rank p = 0.013). In a logistic regression model, MR-proANP was identified as the best predictor of survival. Adding MR-proANP and PCT to SAPS II and SOFA improved their predictive properties (area under the curve 0.895 and 0.880). We conclude that the combination of two biomarkers, MR-proANP and PCT, improve survival prediction of clinical severity scores in VAP.