Udo Kaisers

Critical illness polyneuropathy and myopathy in patients with acute respiratory distress syndrome.

Objective:Critical illness polyneuropathy/myopathy (CIP/CIM) is frequently described in critically ill patients who survive severe sepsis. Clinically relevant paresis is major symptom of CIP/CIM. We aimed at determining risk factors and diagnostic value of electrophysiologic testing for CIP/CIM in patients with acute respiratory distress syndrome (ARDS). Design:Single-center, retrospective analysis, using charts. Setting:University medical center. Patients:Fifty consecutive ARDS patients in our intensive care unit. Interventions:Patient characteristics and clinical course were analyzed. All patients received early electrophysiologic testing. CIP/CIM was diagnosed by the presence of clinical relevant paresis. Measurements and Main Results:Clinically relevant paresis was confirmed in 27 ARDS patients (60%), whereas in 18 patients no paresis was determined (controls); five patients died before clinical assessment of paresis was feasible. Patients with paresis were older, had more days on mechanical ventilation, and had increased intensive care unit length of stay compared with controls. Patients who developed paresis had elevated daily peak blood glucose levels during 28 days of intensive care unit treatment: 166 (134, 200) mg/dL in CIP/CIM patients vs. 144 (132, 161) mg/dL in controls (median, quartiles). Twenty-five of 27 patients with paresis revealed reduced motor unit potentials, fibrillation potentials, or positive sharp waves on early electrophysiologic testing indicating CIP/CIM, whereas 16 of 18 control patients did not. Conclusions:In ARDS patients, paresis is a frequent complication causing prolonged mechanical ventilation and intensive care unit length of stay. An association between hyperglycemia and CIP/CIM has been found. However, since this is a retrospective survey, a causal relation is not clearly supported. In this study, the use of early electrophysiologic testing in ARDS patients was a valuable diagnostic tool for detecting CIP/CIM.

High-Protein Enteral Nutrition Enriched With Immune-Modulating Nutrients vs Standard High-Protein Enteral Nutrition and Nosocomial Infections in the ICU: A Randomized Clinical Trial

IMPORTANCE Enteral administration of immune-modulating nutrients (eg, glutamine, omega-3 fatty acids, selenium, and antioxidants) has been suggested to reduce infections and improve recovery from critical illness. However, controversy exists on the use of immune-modulating enteral nutrition, reflected by lack of consensus in guidelines. OBJECTIVE To determine whether high-protein enteral nutrition enriched with immune-modulating nutrients (IMHP) reduces the incidence of infections compared with standard high-protein enteral nutrition (HP) in mechanically ventilated critically ill patients. DESIGN, SETTING, AND PARTICIPANTS The MetaPlus study, a randomized, double-blind, multicenter trial, was conducted from February 2010 through April 2012 including a 6-month follow-up period in 14 intensive care units (ICUs) in the Netherlands, Germany, France, and Belgium. A total of 301 adult patients who were expected to be ventilated for more than 72 hours and to require enteral nutrition for more than 72 hours were randomized to the IMHP (n = 152) or HP (n = 149) group and included in an intention-to-treat analysis, performed for the total population as well as predefined medical, surgical, and trauma subpopulations. INTERVENTIONS High-protein enteral nutrition enriched with immune-modulating nutrients vs standard high-protein enteral nutrition, initiated within 48 hours of ICU admission and continued during the ICU stay for a maximum of 28 days. MAIN OUTCOMES AND MEASURES The primary outcome measure was incidence of new infections according to the Centers for Disease Control and Prevention (CDC) definitions. Secondary end points included mortality, Sequential Organ Failure Assessment (SOFA) scores, mechanical ventilation duration, ICU and hospital lengths of stay, and subtypes of infections according CDC definitions. RESULTS There were no statistically significant differences in incidence of new infections between the groups: 53% (95% CI, 44%-61%) in the IMHP group vs 52% (95% CI, 44%-61%) in the HP group (P = .96). No statistically significant differences were observed in other end points, except for a higher 6-month mortality rate in the medical subgroup: 54% (95% CI, 40%-67%) in the IMHP group vs 35% (95% CI, 22%-49%) in the HP group (P = .04), with a hazard ratio of 1.57 (95% CI, 1.03-2.39; P = .04) for 6-month mortality adjusted for age and Acute Physiology and Chronic Health Evaluation II score comparing the groups. CONCLUSIONS AND RELEVANCE Among adult patients breathing with the aid of mechanical ventilation in the ICU, IMHP compared with HP did not improve infectious complications or other clinical end points and may be harmful as suggested by increased adjusted mortality at 6 months. These findings do not support the use of IMHP nutrients in these patients. TRIAL REGISTRATION trialregister.nl Identifier: NTR2181.

Secondary insults in severe head injury: Do multiply injured patients do worse?

Objectives To study the occurrence of secondary insults and the influence of extracranial injuries on cerebral oxygenation and outcome in patients with closed severe head injury (Glasgow Coma Scale score ≤8). Design Two-year prospective, clinical study. Setting Two intensive care units in a level III trauma center. Patients We studied 119 patients. Eighty patients had severe head injury and were divided into two categories: “isolated” severe head injury patients (n = 36, Injury Severity Score <30), and severe head injury patients with associated extracranial injuries (n = 44, Injury Severity Score >29). Thirty-nine patients with extracranial injuries and no head injury served as the control group. Interventions After patients were admitted to the intensive care unit, we began continuous multimodal cerebral monitoring of intracranial pressure, mean arterial blood pressure, cerebral perfusion pressure, end-tidal Co2 , brain tissue Po2 (Licox), jugular bulb oxyhemoglobin saturation in severe head injury patients, and mean arterial blood pressure in the control group. Targets of management included intracranial pressure <20 mm Hg, cerebral perfusion pressure >60 mm Hg, Paco2 > 30 mm Hg, control of cerebral oxygenation, and delayed surgery for non-life-threatening extracranial lesions. Measurements and Main Results Data were analyzed for critical thresholds. The occurrence of secondary insults (intracranial pressure >20 mm Hg, mean arterial blood pressure <70 mm Hg, cerebral perfusion pressure <60 mm Hg, end-tidal Co2 <30 torr, brain tissue Po2 <10 torr, jugular bulb oxyhemoglobin saturation <50%) was comparable in patients with isolated severe head injury and those with severe head injury with associated extracranial lesions (Abbreviated Injury Scale score ≤5). The duration of intracranial hypertension and arterial hypotension significantly correlated with an unfavorable outcome, independent of the Injury Severity Score. In patients with severe head injury, 1-yr outcome was 29% dead or vegetative, 17% severely disabled, and 54% moderate or good outcome. This was similar to patients with severe head injury and extracranial injuries (31% dead or vegetative, 14% severely disabled, and 56% moderate or good outcome) and was independent of the Injury Severity Score. Patients with no head injury had less secondary insults (mean arterial blood pressure <70 mm Hg, p < .01) and a better outcome compared with both severe head injury groups (p < .044). Conclusions In patients with severe head injury who have targeted management including intracranial pressure- and cerebral perfusion pressure-guided therapy and delayed surgery for extracranial lesions, the occurrence of secondary insults in the intensive care unit and long-term neurological outcome were comparable and independent of the presence of extracranial lesions (Abbreviated Injury Severity level ≤5). A severe head injury is still a major contributor predicting an unfavorable outcome in multiply injured patients.

Rapid emergence of secondary resistance to gentamicin and colistin following selective digestive decontamination in patients with KPC-2-producing Klebsiella pneumoniae: a single-centre experience

After a single patient was transferred to Leipzig University Hospital from a hospital in Rhodes, Greece, the hospital experienced the largest outbreak due to a KPC-2-producing Klebsiella pneumoniae (KPC-2-KP) strain thus far observed in Germany. Ninety patients hospitalised between July 2010 and October 2012 were affected. In an attempt to eliminate KPC-2-KP from their digestive tracts, 14 consecutive patients (16%) were treated with a short course (7 days) of selective digestive decontamination (SDD), employing colistin (1 million units q.i.d.) and gentamicin (80 mg q.i.d.) as oral solutions, and applying colistin/gentamicin gel (0.5 g) to the oral cavity. In a retrospective analysis, these 14 SDD patients were compared with the remaining 76 patients harbouring KPC-2-KP. KPC-2-KP carrier status was followed in all 14 SDD patients by submitting stool samples to KPC-specific PCR. The mean follow-up period was 48 days (range 12-103 days). Successful elimination of KPC-2-KP was defined as a minimum of three consecutive negative PCR test results separated by ≥48 h each. Decolonisation of KPC-2-KP was achieved in 6/14 patients (43%) after a mean of 21 days (range 12-40 days), but was also observed in 23/76 (30%) of the non-SDD controls (P = 0.102). SDD treatment resulted in the development of secondary resistance to colistin (19% increase in resistance rate) and gentamicin (45% increase) in post-treatment isolates. In the control group, no secondary resistance occurred. We conclude that the SDD protocol applied in this study was not sufficiently effective for decolonisation and was associated with resistance development.

Effect of Sodium Selenite Administration and Procalcitonin-Guided Therapy on Mortality in Patients With Severe Sepsis or Septic Shock: A Randomized Clinical Trial

IMPORTANCE High-dose intravenous administration of sodium selenite has been proposed to improve outcome in sepsis by attenuating oxidative stress. Procalcitonin-guided antimicrobial therapy may hasten the diagnosis of sepsis, but effect on outcome is unclear. OBJECTIVE To determine whether high-dose intravenous sodium selenite treatment and procalcitonin-guided anti-infectious therapy in patients with severe sepsis affect mortality. DESIGN, SETTING, AND PARTICIPANTS The Placebo-Controlled Trial of Sodium Selenite and Procalcitonin Guided Antimicrobial Therapy in Severe Sepsis (SISPCT), a multicenter, randomized, clinical, 2 × 2 factorial trial performed in 33 intensive care units in Germany, was conducted from November 6, 2009, to June 6, 2013, including a 90-day follow-up period. INTERVENTIONS Patients were randomly assigned to receive an initial intravenous loading dose of sodium selenite, 1000 µg, followed by a continuous intravenous infusion of sodium selenite, 1000 µg, daily until discharge from the intensive care unit, but not longer than 21 days, or placebo. Patients also were randomized to receive anti-infectious therapy guided by a procalcitonin algorithm or without procalcitonin guidance. MAIN OUTCOMES AND MEASURES The primary end point was 28-day mortality. Secondary outcomes included 90-day all-cause mortality, intervention-free days, antimicrobial costs, antimicrobial-free days, and secondary infections. RESULTS Of 8174 eligible patients, 1089 patients (13.3%) with severe sepsis or septic shock were included in an intention-to-treat analysis comparing sodium selenite (543 patients [49.9%]) with placebo (546 [50.1%]) and procalcitonin guidance (552 [50.7%]) vs no procalcitonin guidance (537 [49.3%]). The 28-day mortality rate was 28.3% (95% CI, 24.5%-32.3%) in the sodium selenite group and 25.5% (95% CI, 21.8%-29.4%) (P = .30) in the placebo group. There was no significant difference in 28-day mortality between patients assigned to procalcitonin guidance (25.6% [95% CI, 22.0%-29.5%]) vs no procalcitonin guidance (28.2% [95% CI, 24.4%-32.2%]) (P = .34). Procalcitonin guidance did not affect frequency of diagnostic or therapeutic procedures but did result in a 4.5% reduction of antimicrobial exposure. CONCLUSIONS AND RELEVANCE Neither high-dose intravenous administration of sodium selenite nor anti-infectious therapy guided by a procalcitonin algorithm was associated with an improved outcome in patients with severe sepsis. These findings do not support administration of high-dose sodium selenite in these patients; the application of a procalcitonin-guided algorithm needs further evaluation. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00832039.

Effects of Music Listening on Cortisol Levels and Propofol Consumption during Spinal Anesthesia

Background: This study explores effects of instrumental music on the hormonal system (as indicated by serum cortisol and adrenocorticotropic hormone), the immune system (as indicated by immunoglobulin A) and sedative drug requirements during surgery (elective total hip joint replacement under spinal anesthesia with light sedation). This is the first study investigating this issue with a double-blind design using instrumental music. Methodology/Principal Findings: Patients (n = 40) were randomly assigned either to a music group (listening to instrumental music), or to a control group (listening to a non-musical placebo stimulus). Both groups listened to the auditory stimulus about 2 h before, and during the entire intra-operative period (during the intra-operative light sedation, subjects were able to respond lethargically to verbal commands). Results indicate that, during surgery, patients of the music group had a lower propofol consumption, and lower cortisol levels, compared to the control group. Conclusion/Significance: Our data show that listening to music during surgery under regional anesthesia has effects on cortisol levels (reflecting stress-reducing effects) and reduces sedative requirements to reach light sedation.

Selective pulmonary vasodilation in acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is characterized by a marked maldistribution of pulmonary perfusion in favor of nonventilated, atelectatic areas of the lungs, and it is the main cause of pulmonary right-to-left shunting and hypoxemia. Therapeutic interventions to selectively influence pulmonary perfusion in ARDS became feasible with the introduction of inhaled nitric oxide, which provided a means not only to reduce pulmonary hypertension, but also to improve matching of ventilation to perfusion and, thus, hypoxemia. Clinical studies in ARDS subsequently demonstrated that the combination of inhaled nitric oxide with other interventions, such as positive end-expiratory pressure and prone positioning, yielded beneficial and additive effects on arterial oxygenation. Although the available randomized, controlled trials of this novel concept have so far failed to show an improved outcome in ARDS, inhaled nitric oxide is a clinically valuable option for the treatment of severe refractory hypoxemia in ARDS, and largely promoted the concept of selective pulmonary vasodilation in intensive care practice. Currently, aerosolization of various vasodilators, in particular prostaglandins, is under evaluation in models of acute lung injury and human ARDS. Ongoing research aims to augment the effectiveness of vasodilators with specific inhibitors of phosphodiesterases or by combination with intravenous vasoconstrictors. Consequently, several alternative ways to selectively modulate pulmonary vascular tone in patients with ARDS may be available in the near future. Cost-benefit analysis of these therapeutic options will largely determine their future perspective.

Long-term carriage of Klebsiella pneumoniae carbapenemase-2-producing K pneumoniae after a large single-center outbreak in Germany.

BACKGROUND The natural progress of intestinal colonization with Klebsiella pneumoniae carbapenemase-2-producing K pneumoniae (KPC-2-KP) is almost unknown. METHODS After a large, single-center outbreak of KPC-2-KP, we analyzed carrier prevalence through retrospective and prospective investigation of intestinal KPC-2-KP carriage 1 month, 3 months, 6 months, 1 year, and 2 years after acquisition, defined as the earliest date of KPC-2-KP detection. Rectal swabs or stool samples were collected at baseline and at each visit and submitted for both culture and KPC-specific polymerase chain reaction. Resolution of intestinal KPC-2-KP carriage was defined as a minimum of 3 consecutive negative polymerase chain reaction test results separated by at least 48 hours. RESULTS In patients available for long-term evaluation 26 out of 84 patients (31%) tested negative for KPC-2-KP after 1 month, 14 out of 34 (41%) after 3 months, 17 out of 26 (65%) after 6 months, 14 out of 19 (74%) after 1 year, and 5 out of 6 (83%) after 2 years. Decolonization of KPC-2-KP was hampered in patients with prolonged or repeated hospitalization (P = .044-.140, depending on the time interval). Two patients retested positive for KPC-2-KP after they had previously shown 3 consecutive negative tests. The longest positive KPC-2-KP carrier status so far was observed after nearly 40 months (1,191 days). CONCLUSIONS The majority of patients experienced spontaneous decolonization within 6 months after acquisition, mainly after discharge from the hospital. However, long-term carriage of >3 years is possible. Appropriate infection control measures must be taken when these patients are readmitted to health care facilities. A series of at least 4 consecutive negative rectal swabs or stool samples separated by sufficient time intervals appears necessary before the declaration of successful KPC-2-KP decolonization is made.

Do Variations in the 5-ht3a and 5-ht3b Serotonin Receptor Genes ( htr3a and htr3b ) Influence the Occurrence of Postoperative Vomiting?

BACKGROUND: Postoperative nausea and vomiting are unpleasant side effects of general anesthesia. Besides known risk factors (female gender, nonsmoker, history, and opioids), a genetic influence of the serotonin receptor system on the development of nausea and vomiting has repeatedly been proposed. In this pilot study, we therefore investigated the genes of the serotonin receptor subunits A and B (HTR3A and HTR3B) for genetic variants. METHODS: We included 95 patients who had suffered from postoperative vomiting (POV) after general anesthesia and 94 control patients. After DNA isolation, the entire HTR3A and HTR3B coding regions, the 5′ flanking regions, and exon/intron boundaries were screened for genetic variants. Correlation of identified genetic variants with POV was determined by logistic regression. RESULTS: We identified 16 different variants in the HTR3A gene and 19 in the HTR3B gene. By using a multivariate logistic regression model that also included classical risk factors, the HTR3A variant c1377A>G was associated with a significantly higher risk (odds ratio [OR] 2.972; 95% confidence interval [CI] 1.466–6.021; P = 0.003) and the HTR3B variants c5+201_+202delCA (OR 0.421; 95% CI 0.257–0.69; P = 0.001) and c6-137C>T (OR 0.034; 95% CI 0.003–0.332; P = 0.004) were associated with a lower risk for POV. However, all significant genetic variants were located in noncoding regions of their gene. CONCLUSIONS: Genetic variations in the HTR3A and HTR3B gene seem to be associated with the individual risk of developing POV. How strong their influence is within the multifactorial genesis of POV needs to be investigated in additional studies with an appropriate sample size.

Cerebrospinal Fluid Melanin-Concentrating Hormone (MCH) and Hypocretin-1 (HCRT-1, Orexin-A) in Alzheimer’s Disease

Ancillary to decline in cognitive abilities, patients with Alzheimer’s disease (AD) frequently suffer from behavioural and psychological symptoms of dementia (BPSD). Hypothalamic polypeptides such as melanin-concentrating hormone (MCH) and hypocretin-1 (HCRT-1, orexin-A) are promoters of sleep-wake regulation and energy homeostasis and are found to impact on cognitive performance. To investigate the role of MCH and HCRT-1 in AD, cerebrospinal fluid (CSF) levels were measured in 33 patients with AD and 33 healthy subjects (HS) using a fluorescence immunoassay (FIA). A significant main effect of diagnosis (F(1,62) = 8.490, p<0.01) on MCH levels was found between AD (93.76±13.47 pg/mL) and HS (84.65±11.40 pg/mL). MCH correlated with T-tau (r = 0.47; p<0.01) and P-tau (r = 0.404; p<0.05) in the AD but not in the HS. CSF-MCH correlated negatively with MMSE scores in the AD (r = −0.362, p<0.05) and was increased in more severely affected patients (MMSE≤20) compared to HS (p<0.001) and BPSD-positive patients compared to HS (p<0.05). In CSF-HCRT-1, a significant main effect of sex (F(1,31) = 4.400, p<0.05) with elevated levels in females (90.93±17.37 pg/mL vs. 82.73±15.39 pg/mL) was found whereas diagnosis and the sex*diagnosis interaction were not significant. Elevated levels of MCH in patients suffering from AD and correlation with Tau and severity of cognitive impairment point towards an impact of MCH in AD. Gender differences of CSF-HCRT-1 controversially portend a previously reported gender dependence of HCRT-1-regulation. Histochemical and actigraphic explorations are warranted to further elucidate alterations of hypothalamic transmitter regulation in AD.