Dimitrios Zervakis

Electrical muscle stimulation prevents critical illness polyneuromyopathy: a randomized parallel intervention trial

IntroductionCritical illness polyneuromyopathy (CIPNM) is a common complication of critical illness presenting with muscle weakness and is associated with increased duration of mechanical ventilation and weaning period. No preventive tool and no specific treatment have been proposed so far for CIPNM. Electrical muscle stimulation (EMS) has been shown to be beneficial in patients with severe chronic heart failure and chronic obstructive pulmonary disease. Aim of our study was to assess the efficacy of EMS in preventing CIPNM in critically ill patients.MethodsOne hundred and forty consecutive critically ill patients with an APACHE II score ≥ 13 were randomly assigned after stratification to the EMS group (n = 68) (age:61 ± 19 years) (APACHE II:18 ± 4, SOFA:9 ± 3) or to the control group (n = 72) (age:58 ± 18 years) (APACHE II:18 ± 5, SOFA:9 ± 3). Patients of the EMS group received daily EMS sessions. CIPNM was diagnosed clinically with the medical research council (MRC) scale for muscle strength (maximum score 60, <48/60 cut off for diagnosis) by two unblinded independent investigators. Duration of weaning from mechanical ventilation and intensive care unit (ICU) stay were recorded.ResultsFifty two patients could be finally evaluated with MRC; 24 in the EMS group and 28 in the control group. CIPNM was diagnosed in 3 patients in the EMS group as compared to 11 patients in the control group (OR = 0.22; CI: 0.05 to 0.92, P = 0.04). The MRC score was significantly higher in patients of the EMS group as compared to the control group [58 (33 to 60) vs. 52 (2 to 60) respectively, median (range), P = 0.04). The weaning period was statistically significantly shorter in patients of the EMS group vs. the control group [1 (0 to 10) days vs. 3 (0 to 44) days, respectively, median (range), P = 0.003].ConclusionsThis study suggests that daily EMS sessions prevent the development of CIPNM in critically ill patients and also result in shorter duration of weaning. Further studies should evaluate which patients benefit more from EMS and explore the EMS characteristics most appropriate for preventing CIPNM.Trial Registration NumberClinicalTrials.gov NCT00882830

Effect of Clarithromycin in Patients with Sepsis and Ventilator-Associated Pneumonia

BACKGROUND Because clarithromycin provided beneficiary nonantibiotic effects in experimental studies, its efficacy was tested in patients with sepsis and ventilator-associated pneumonia (VAP). METHODS Two hundred patients with sepsis and VAP were enrolled in a double-blind, randomized, multicenter trial from June 2004 until November 2005. Clarithromycin (1 g) was administered intravenously once daily for 3 consecutive days in 100 patients; another 100 patients were treated with placebo. Main outcomes were resolution of VAP, duration of mechanical ventilation, and sepsis-related mortality within 28 days. RESULTS The groups were well matched with regard to demographic characteristics, disease severity, pathogens, and adequacy of the administered antimicrobials. Analysis comprising 141 patients who survived revealed that the median time for resolution of VAP was 15.5 days and 10.0 days among placebo- and clarithromycin-treated patients, respectively (P = .011); median times for weaning from mechanical ventilation were 22.5 days and 16.0 days, respectively (p = .049). Analysis comprising all enrolled patients showed a more rapid decrease of the clinical pulmonary infection score and a delay for advent of multiple organ dysfunction in clarithromycin-treated patients, compared with those of placebo-treated patients (p = .047). Among the 45 patients who died of sepsis, time to death was significantly prolonged in clarithromycin-treated compared with placebo-treated patients (p = .004). Serious adverse events were observed in 0% and 3% of placebo- and clarithromycin-treated patients, respectively (P = .25). CONCLUSIONS Clarithromycin accelerated the resolution of VAP and weaning from mechanical ventilation in surviving patients and delayed death in those who died of sepsis. The mortality rate at day 28 was not altered. Results are encouraging and render new perspectives on the management of sepsis and VAP.

Short-term Systemic Effect of Electrical Muscle Stimulation in Critically Ill Patients

BACKGROUND Our study assessed the short-term effect of electrical muscle stimulation (EMS) of the lower extremities on the thenar muscle microcirculation of patients who are critically ill. METHODS Twenty-nine hospital ICU patients (19 men; mean [+/- SD] age, 58 +/- 19 years; mean acute physiology and chronic health evaluation score, 17 +/- 5; mean sequential organ failure assessment score, 9 +/- 3) underwent a 45-min session of EMS of the lower extremities. BP and heart rate were measured, and blood samples were retrieved. Tissue oxygen saturation (Sto(2)) was assessed with near infrared spectroscopy at the thenar muscle with a vascular occlusion before and after EMS. A control group of six patients who were critically ill (4 men; mean age, 50 +/- 19 years) also were included in the study. RESULTS The mean Sto(2) did not differ significantly before and after the EMS session (81 +/- 16% vs 83 +/- 16%, respectively). The oxygen consumption rate during vascular occlusion differed significantly before the beginning and at the end of the session (20 +/- 9%/min vs 22 +/- 9%/min, respectively; p < 0.05). The reperfusion rate differed significantly before the beginning and at the end of the session (299 +/- 177%/min vs 375 +/- 182%/min, respectively; p < 0.05). Heart rate increased significantly at the end of the session (94 +/- 16 beats/min vs 99 +/- 16 beats/min, respectively; p < 0.05) as did systolic BP (127 +/- 21 mm Hg vs 133 +/- 23 mm Hg; p < 0.05, respectively). The Sto(2) value did not differ between the two measurements in control patients. CONCLUSION The data suggest that EMS has a systemic effect on microcirculation. These results suggest that further studies are needed to explore the potential use of EMS as a preventive and rehabilitation tool in critically ill patients.

Early apoptosis of blood monocytes in the septic host: is it a mechanism of protection in the event of septic shock?

IntroductionBased on the central role of the triggering of monocytes for the initiation of the septic cascade, it was investigated whether apoptosis of blood monocytes in septic patients is connected to their final outcome.MethodsBlood monocytes were isolated from 90 patients with septic syndrome due to ventilator-associated pneumonia on days 1, 3, 5 and 7 from the initiation of symptoms. Apoptosis was defined after incubation with annexin-V-fluorescein isothiocyanate and propidium iodine and reading by a flow cytometer. The function of first-day monocytes was evaluated from the concentrations of tumour necrosis factor alpha (TNFα) and IL-6 in supernatants of cell cultures after triggering with endotoxins. TNFα, IL-6 and IL-8 were estimated in serum by an enzyme immunoassay.ResultsMortality rates of patients with apoptosis ≤50% compared with patients with apoptosis >50% were 49.12% and 15.15%, respectively (P < 0.0001). Kaplan-Meier analysis showed a 28-day survival benefit in patients with septic shock and monocyte apoptosis >50% compared with those patients with apoptosis ≤50% (P = 0.0032). Production of IL-6 by monocytes on the first day by patients with apoptosis ≤50% was similar compared with monocytes isolated from healthy controls. Serum concentrations of TNFα were higher in patients with monocyte apoptosis ≤50% and septic shock compared with patients with apoptosis >50% on day 7; similar findings occurred for serum IL-6 on days 1 and 7 and for serum IL-8 on days 1 and 5.ConclusionEarly apoptosis of monocytes upon presentation of clinical signs of sepsis is connected to a favourable outcome. These findings are of particular importance for the patient with septic shock, where they might constitute a mechanism of pathogenesis.

Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: A lethal cause of pneumonia in an adult immunocompetent patient

Necrotizing pneumonia and fatal septic shock were caused by Panton-Valentine leukocidin-positive, community-acquired, methicillin-resistant Staphylococcus aureus (CA-MRSA) in a previously healthy, 61-y-old female. This patient did not belong to any high-risk group (e.g. homosexuals, military recruits, sports team members, etc.). CA-MRSA infection should be suspected in any adult with severe pneumonia/sepsis.

Kinetics of progenitor hemopoetic stem cells in sepsis: Correlation with patients survival?

BackgroundCurrent theories underline the crucial role of pro-inflammatory mediators produced by monocytes for the pathogenesis of sepsis. Since monocytes derive from progenitor hemopoetic cells, the kinetics of stem cells was studied in peripheral blood of patients with sepsis.MethodsBlood was sampled from 44 patients with septic syndrome due to ventilator-associated pneumonia on days 1, 3, 5 and 7 upon initiation of symptoms. Concentrations of tumour necrosis factor-alpha (TNFα), interleukin (IL)-6, IL-8 and G-CSF were estimated by ELISA. CD34/CD45 cells were determined after incubation with anti-CD45 FITC and anti-CD34 PE monocloncal antibodies and flow cytometric analysis. Samples from eight healthy volunteers served as controls.ResultsMedian of CD34/CD45 absolute count of controls was 1.0/μl. Respective values of the total study population were 123.4, 112.4, 121.5 and 120.9/μl on days 1, 3, 5 and 7 (p < 0.0001 compared to controls). Positive correlations were found between the absolute CD34/CD45 count and the absolute monocyte count on days 1, 5 and 7. Survival was prolonged among patients with less than 310/μl CD34/CD45 cells on day 1 compared to those with more than 310/μl of CD34/CD45 cells (p: 0.022). Hazard ratio for death due to sepsis was 5.47 (p: 0.039) for CD34/CD45 cells more than 310/μl. Median IL-6 on day 1 was 56.78 and 233.85 pg/ml respectively for patients with less than 310/μl and more than 310/μl CD34/CD45 cells (p: 0.021).ConclusionStem cells are increased in peripheral blood over all days of follow-up compared to healthy volunteers. Patients with counts on day 1 less than 310/μl are accompanied by increased survival compared to patients with more than 310/μl.

MELAS syndrome diagnosed in ICU in a 56-year-old patient presenting with status epilepticus.

The differential diagnosis of stroke in a middle-aged adult usually does not include the mitochondrial myopathy, encephalopathy, lactic acidosis and strokelike episodes syndrome (MELAS), because such a manifestation very rarely first occurs after the age of 40 [1, 2]. We report the case of a 56-year-old woman, brought to our hospital with irritability, aphasia, and ataxic gait. A brain computed tomography revealed a hypodense area on the left temporal lobe (Fig. 1). Ten hours later she developed convulsive status epilepticus and loss of consciousness. She was treated with phenytoin and transferred to the ICU, mechanically ventilated and sedated with propofol. Her past medical history was marked for a hearing deficit, for which a cochlear implant had been inserted 2 years earlier, and for an episode of loss of consciousness 6 months earlier. She was functional with daily activities. The patient was childless. Three out of her four sisters had died at early age. On ICU admission, physical examination revealed right hemiparesis. Pupils were equal and reactive and vital signs were within normal range. Fundoscopic examination was normal. Laboratory parameters were unremarkable, with the exception of white-cell count 18,900/mm (85 % neutrophils), aspartate aminotransferase 274 U/L, alanine aminotransferase 82 U/L, creatine kinase 9,705 U/L and lactate 3.3 mmol/L. Cerebrospinal fluid (CSF) examination was normal. The electroencephalogram showed frequent temporal spikes and slow wave complexes. Extensive imaging for brain vascular disease and laboratory investigation for autoimmune or infectious brain disease all proved negative. Magnetic resonance imaging was avoided due to the presence of the cochlear implant. On ICU day 7, the patient remained comatose. Persistent elevated blood lactate (2.5–5.3 mmol/L) was noted, despite clinical absence of seizures or haemodynamic instability. Repeat CSF revealed lactate 4.3 mmol/ L, not measured in the first sample. A mitochondrial encephalopathy was then suspected. A quadriceps muscle biopsy specimen revealed ‘‘ragged red fibres’’, corroborating the diagnosis of MELAS. Relatives declined further investigation with mitochondrial DNA analysis because the result would not affect the patient’s management, and there was no reason for genetic counseling. The patient had a slow neurological improvement; she weaned from mechanical ventilation and 44 days after ICU admission she was transferred to a rehabilitation center with a Glasgow Coma Scale of 13. First described in 1984, MELAS is a rare, maternally inherited clinical entity resulting from mutations in the mitochondrial DNA [1, 2]. The term ‘‘strokelike’’ refers to clinical and radiological impression of brain ischemia, albeit not conformed to a vascular territory. Although their pathogenesis remains unclear, relative deficiency of cellular adenosine triphoshate has been implicated [3]. According to diagnostic criteria, ‘‘strokelike’’ episodes have to appear before the age of 40 [2]. Few cases occur after the age of 50 [2–5] and none was first diagnosed in the ICU setting. Partial and complex partial status epilepticus are more commonly seen than generalized convulsive status epilepticus in MELAS [6]. ICU

Left atrial giant thrombus infected by Escherichia Coli. Case report

BackgroundLeft atrial thrombi are mostly related to mitral valve disease. The differential diagnosis of clots and myxomas in the left atrium is mostly based on echocardiography. Infection of intracardiac thrombi is extremely rare and mostly reported in ventricular clots or aneurysms following myocardial infarction.Case presentationWe present the case of a 65 year old female with a history of mitral valve disease and chronic atrial fibrillation who suffered repeated embolic strokes and a giant infected clot in the left atrium. Although the patient underwent prompt surgery with removal of the clot and valve replacement the complication of septic emboli to the CNS led her to death. To the best of our knowledge this is the second report of an infected left atrial thrombus.ConclusionThe case is a representative example of a neglected and undertreated patient with catastrophic consequences. Anticoagulant therapy in patients with mitral valve disease and atrial fibrillation should be applied according the currently available guidelines and standards in order to avoid analogous paradigms in the future. Mitral valve substitution should be considered in patients with mitral valve disease presenting thromboembolic complications. Surgery should be considered as the treatment of choice in cases of organized left atrial thrombus and suspected tumor or infected mass.

HSV presence in the CSF of a head trauma patient : Cause or result?

Dear Editor, I would like to comment on our experience of a curious head trauma case. During August 2004, we admitted a 21-y-old male patient after a motor vehicle accident. His medical history was unremarkable apart from multiple herpes labialis eruptions and heavy alcohol abuse. His GCS on admission was 6 (E1, M3, V1) and brain CT scan revealed right parietal-occipital speckled hyperdense lesions compatible with tiny brain contusions or small foci of subarachnoid haemorrhage, a small amount of blood in the occipital left ventral horn and slight brain oedema. There were also hethmoid bone fractures and a small left hemothorax. He remained intubated for 19 d because of poor neurological performance and fever, the latter being attributed to left lower lobe (ventilator associated) pneumonia initially and later to sinusitis. He received antibiotics and underwent sinus drainage. The fever was persistent, ranging from 38 to 398C. On extubation his GCS was 9 (E3, M5, V1) but still there was discordance with the brain appearance on last CT, which had no pathological signs apart from the presence of small frontal hygromas. At that time a full CNS investigation was undertaken: lumbar puncture showed pleocytosis with 575 cells/mm, 95% lymphocytes, 5 erythrocytes/mm, 158 mg/dl protein and 111 mg/dl glucose. Brain MRI disclosed a linear hyperdense lesion on the left temporal lobe and HEG conducted under anticonvulsant therapy disclosed diffuse slow D rhythm. Although Gram stain and CSF culture was negative the patient was treated with meropenem with the working diagnosis of residual meningitis due to undiagnosed CSF leakage through the skull fractures. Unexpectedly, PCR for HSV type 1 in the CSF was positive and acyclovir was added to the antibiotic regimen. The fever and mental status of the patient gradually improved concordant with the HEG and CSF findings improvement during the next 15 d. He was discharged with a GCS of 15 on the 35th d. Given the high specificity of PCR assays for the presence of HSV genome in the cerebrospinal fluid, the typical CSF lymphocytosis without the presence of corresponding erythrocytes and the absence of obvious leakage, we tend to accept the diagnosis of viral insult to the brain either as the cause of the accident or as viral reactivation due to cranial trauma. Both are only rarely described in the literature [1 4] and emphasize the need for diagnosis re-evaluation and thorough investigation from zero basis when clinical course is not satisfactory.