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Biomedical subjects

Tarek Sharshar

Publications and source records attributed to Tarek Sharshar.

At least 19 recordsLinked to original sources
PubMed2006

Prognosis and risk factors of early onset pneumonia in ventilated patients with Guillain-Barré syndrome.

OBJECTIVE: Invasive mechanical ventilation is required in 30% of patients with Guillain-Barré syndrome (GBS) and is associated with pneumonia and increased mortality. Our objective was to determine the incidence, characteristics, outcomes, and risk factors of pneumonia in GBS patients receiving mechanical ventilation. DESIGN AND SETTING: Study of a prospective database in an intensive care unit of a university hospital. PATIENTS: The study included 81 patients who required intubation for GBS. Neurological findings, vital capacity, and signs of respiratory distress were recorded at admission and at intubation. A score predicting the risk of intubation (0-4) was calculated for each patient. Pneumonia was diagnosed based on predefined criteria and retrospectively confirmed by two observers. Early-onset pneumonia was defined as pneumonia diagnosed within 5 days after intubation. MEASUREMENTS AND RESULTS: Mean vital capacity was 57 +/- 22% of predicted at admission and 33 +/- 11% at intubation. Pneumonia developed in 63 patients (78%), including 48 with early-onset pneumonia. Bacteria were consistent with aspiration. Of the 63 patients with pneumonia 11 (18%) had septic shock, 6 (10%) had acute respiratory distress syndrome, and 9 (14%) died. In the univariate analysis milder weakness, a lower risk of intubation (score < 2), and time from admission to intubation longer than 2 days were associated with early-onset pneumonia. Time from admission to intubation was the only independent predictor in the multivariate logistic regression model. CONCLUSIONS: Early-onset pneumonia is a common and severe complication that is related to aspiration in patients with GBS. Delaying intubation may increase the risk of early-onset pneumonia.

APACHE↗
PubMed2006

Exercise-induced depression of the diaphragm motor evoked potential is not affected by non-invasive ventilation.

Whole body exercise is followed by a depression of the diaphragm motor evoked potential (MEP). It is unknown whether the change is due to diaphragm activity or whole body exercise. To test the hypothesis that exercise-induced MEP depression was related to diaphragm activity, we performed two experiments. The first examined the effect of whole body exercise, performed with and without the use of non-invasive ventilation (NIV). NIV resulted in significant unloading of the diaphragm (pressure time product 101+/-68 cm H(2)O/s/min versus 278+/-95 cm H(2)O/s/min, p<0.001). Both conditions produced significant MEP depression compared to the control condition (% drop at 5 min, after exercise and exercise with NIV: 29 and 34%, p=0.77). Study 2 compared exercise with isocapnic hyperventilation. At 20 min the MEP had fallen by 29% in the exercise session versus 5% with hyperventilation (p=0.098). We conclude that the work of breathing during whole body exercise is not the primary driver of exercise-induced diaphragm MEP depression.

Adult↗
PubMed2006

Clinical and electrophysiological predictors of respiratory failure in Guillain-Barré syndrome: a prospective study.

BACKGROUND: Respiratory failure is the most serious short-term complication of Guillain-Barré syndrome and can require invasive mechanical ventilation in 20-30% of patients. We sought to identify clinical and electrophysiological predictors of respiratory failure in the disease. METHODS: We prospectively assessed electrophysiological data and clinical factors, including identified predictors of delay between disease onset and admission, inability to lift head, and vital capacity, in patients admitted with Guillain-Barré syndrome. We related these factors to subsequent need for ventilatory support. Neurophysiological findings were classified as demyelinating, axonal, equivocal, unexcitable, or normal. Predictive values of clinical and electrophysiological data were tested using classification trees to build up a predictive model. This model was initially built up in a two-third (fitting set) then validated in a one-third (validation set) of the total sample. The fitting and validation sets were randomly selected. We also assessed the predictive value of this model for disability at 6 months. FINDINGS: From 1998, to 2006, 154 patients with Guillain-Barré syndrome were included in the study and 34 (22%) were subsequently ventilated. Demyelinating Guillain-Barré syndrome was more common in patients who went on to be ventilated than in those who were not (85%vs 51%, p=0.0003). Vital capacity and the proximal/distal compound muscular amplitude potential (p/dCMAP) ratio of the common peroneal nerve were retained in the tree model, with a probability of needing ventilation of less than 2.5% in patients with a ratio of greater than 55.6% and a vital capacity more than 81% of predicted. A p/dCMAP ratio of the peroneal nerve less than 55.6% and age older than 40 years were retained as independent predictors of disability at 6 months. INTERPRETATION: Neurophysiological testing is helpful for assessing risk of respiratory failure, which is highest in patients with evidence of demyelination and very low in those without both 55.6% conduction block of the common peroneal nerve and a 20% reduction in vital capacity.

Action Potentials↗
PubMed2006

Emerging drugs for the treatment of sepsis.

Septic shock still places a major burden on the healthcare system, although recent years have been marked by the demonstration that corticosteroids and activated protein C may substantially improve survival in selected populations. This review discusses the current management of septic shock and the potential development of new therapeutics following impressive advances in the pathomechanisms of septic shock.

Anti-Bacterial Agents↗
PubMed2006

Guillain-Barré syndrome, greater Paris area.

We studied 263 cases of Guillain-Barré syndrome from 1996 to 2001, 40% of which were associated with a known causative agent, mainly Campylobacter jejuni (22%) or cytomegalovirus (15%). The cases with no known agent (60%) peaked in winter, and half were preceded by respiratory infection, influenza-like syndrome, or gastrointestinal illness.

Adult↗
PubMed2005

Does symptom-limited cycle exercise cause low frequency diaphragm fatigue in patients with heart failure?

BACKGROUND: Reduced diaphragm contractility occurs in some healthy subjects when they exercise to exhaustion. This indicates low frequency fatigue, which may contribute to task failure. We hypothesised that patients with congestive heart failure (CHF) might be especially vulnerable to the development of low frequency diaphragm fatigue after exhaustive exercise. AIMS: To study the effect of exhaustive incremental cycle exercise on diaphragm contractility in patients with CHF. METHODS: 12 patients with CHF with an ejection fraction of 36.5 +/- 7.3% and 12 healthy age-matched control subjects performed an incremental cycle test to exhaustion. The unpotentiated twitch transdiaphragmatic pressure (twitch Pdi) in response to bilateral anterolateral magnetic phrenic nerve stimulation (BAMPS) was measured before and after exercise. RESULTS: Twitch Pdi at baseline was 20.2 +/- 6.7 cm H2O in the CHF group and 20.3 +/- .3 cm H2O in the controls (p = 0.957). 25 and 35 min post exercise the values were 19.9+/-5.4 and 20.0+/-5.1 cm H2O in the CHF group and 20.6 +/- 4.3 and 21.2 +/- 3.4 cm H2O in the control group; neither change was significant (F(2,27) = 0.007, p = 0.993; F(2,33) = 0.144, p = 0.866, respectively). CONCLUSION: When patients with CHF cycle to exhaustion, low frequency fatigue of the diaphragm does not occur, and this is unlikely to be an important factor limiting exercise capacity of such patients.

Diaphragm↗
PubMed2005

Motor control of the costal and crural diaphragm--insights from transcranial magnetic stimulation in man.

The costal and crural parts of the diaphragm differ in their embryological development and physiological function. It is not known if this is reflected in differences in their motor cortical representation. We compared the response of the costal and crural diaphragms using varying intensities of transcranial magnetic stimulation of the motor cortex at rest and during submaximal and maximal inspiratory efforts. The costal and crural motor evoked potential recruitment curves during submaximal inspiratory efforts were similar. The response to stimulation before, during and at 10 and 30 min after 44 consecutive maximal inspiratory efforts was also the same. Using paired stimulations to investigate intra-cortical facilitatory and inhibitory circuits we found no difference between the costal and crural response with varying interstimulus intervals, or when conditioning and test stimulus intensity were varied. We conclude that supraspinal control of the costal and crural diaphragm is identical during inspiratory tasks.

Action Potentials↗
PubMed2004

Science review: The brain in sepsis--culprit and victim.

On one side, brain dysfunction is a poorly explored complication of sepsis. On the other side, brain dysfunction may actively contribute to the pathogenesis of sepsis. The current review aimed at summarizing the current knowledge about the reciprocal interaction between the immune and central nervous systems during sepsis. The immune-brain cross talk takes part in circumventricular organs that, being free from blood-brain-barrier, interface between brain and bloodstream, in autonomic nuclei including the vagus nerve, and finally through the damaged endothelium. Recent observations have confirmed that sepsis is associated with excessive brain inflammation and neuronal apoptosis which clinical relevance remains to be explored. In parallel, damage within autonomic nervous and neuroendocrine systems may contribute to sepsis induced organ dysfunction.

Blood-Brain Barrier↗
PubMed2004

Demonstration of a second rapidly conducting cortico-diaphragmatic pathway in humans.

Functional imaging studies in normal humans have shown that the supplementary motor area (SMA) and the primary motor cortex (PMC) are coactivated during various breathing tasks. It is not known whether a direct pathway from the SMA to the diaphragm exists, and if so what properties it has. Using transcranial magnetic stimulation (TMS) a site at the vertex, representing the diaphragm primary motor cortex, has been identified. TMS mapping revealed a second area 3 cm anterior to the vertex overlying the SMA, which had a rapidly conducting pathway to the diaphragm (mean latency 16.7 +/- 2.4 ms). In comparison to the vertex, the anterior position was characterized by a higher diaphragm motor threshold, a greater proportional increase in motor-evoked potential (MEP) amplitude with voluntary facilitation and a shorter silent period. Stimulus-response curves did not differ significantly between the vertex and anterior positions. Using paired TMS, we also compared intracortical inhibition/facilitation (ICI/ICF) curves. In comparison to the vertex, the MEP elicited from the anterior position was not inhibited at short interstimulus intervals (1-5 ms) and was more facilitated at long interstimulus intervals (9-20 ms). The patterns of response were identical for the costal and crural diaphragms. We conclude that the two coil positions represent discrete areas that are likely to be the PMC and SMA, with the latter wielding a more excitatory effect on the diaphragm.

Adult↗
PubMed2004

Corticospinal control of respiratory muscles in chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) face an increased respiratory load and in consequence have an elevated respiratory drive. We used transcranial magnetic stimulation (TMS) to investigate associated changes in corticospinal excitability both at rest and during voluntary facilitation at different levels of inspiratory effort. Diaphragm and abdominal motor thresholds were significantly lower in COPD than healthy controls, but the quadriceps response was the same. In patients there was a significant increase in diaphragm response from rest during 20% inspiratory efforts but no further increase with greater efforts. In controls there was a further stepwise increase at 40% and 60% of inspiratory effort. The cortical silent period was significantly shorter in COPD. Using paired stimulation to study intracortical inhibitory and excitatory circuits we found significantly less excitability of intracortical facilitatory circuits in patients at long (>7 ms) interstimulus intervals. These results suggest that there is a ceiling effect in motor control output to the respiratory muscles of patients with COPD.

Abdominal Muscles↗
PubMed2004

Depression of diaphragm motor cortex excitability during mechanical ventilation.

The effect of mechanical ventilation on the diaphragm motor cortex remains unknown. We assessed the effect of mechanical ventilation on diaphragm motor cortex excitability by measuring the costal and crural diaphragm motor-evoked potential (MEP) elicited by single and paired transcranial magnetic stimulation. In six healthy subjects, MEP recruitment curves of the costal and crural diaphragms were assessed at relaxed end expiration during spontaneous breathing [baseline tidal volume (Vt(baseline))] and isocapnic volume cycled ventilation delivered noninvasively (NIV) at three different levels of tidal volume (Vt(baseline), Vt(baseline) + 5 ml/kg liters, and Vt(baseline) + 10 ml/kg liters). The costal and crural diaphragm response to peripheral stimulation of the right phrenic nerve was not reduced by NIV. NIV reduced the costal and crural MEP amplitude during NIV (P < 0.0001) with the maximal reduction at Vt(baseline) + 5 ml/kg. Response to paired TMS showed that NIV (Vt(baseline) + 5 ml/kg) significantly increased the sensitivity of the cortical motoneurons to facilitatory (>9 ms) interstimulus intervals (P = 0.002), suggesting that the diaphragm MEP amplitude depression during NIV is related to neuromechanical inhibition at the level of motor cortex. Our results demonstrate that mechanical ventilation directly inhibits central projections to the diaphragm.

Abdomen↗
PubMed2004

Does ICU-acquired paresis lengthen weaning from mechanical ventilation?

OBJECTIVE: To determine whether ICU-acquired paresis (ICUAP) is an independent risk factor of prolonged weaning. DESIGN: Second study of a prospective cohort of 95 patients who were enrolled in an incidence and risk factor study of ICUAP. SETTING: Three medical and two surgical ICUs in four hospitals. PATIENTS AND PARTICIPANTS: Ninety-five patients without pre-existing neuromuscular disease recovering from the acute phase of critical illness after > or =7 days of mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Duration of weaning from mechanical ventilation was defined as the duration of mechanical ventilation between awakening (day 1) and successful weaning. Muscle strength was evaluated at day 7 after awakening using the Medical Research Council (MRC) score. Patients with an MRC <48 were considered to have ICUAP. Among the 95 patients (mean age 62.0+/-15.3 years, SAPS 2 on admission 48.7+/-17.4) who regained satisfactory awakening after 7 or more days of mechanical ventilation, 67 (70.5%) were hospitalized in a medical ICU and 28 (29.5%) in a surgical ICU. Median duration (25th-75th percentiles) of weaning was longer in patients with ICUAP than in those without ICUAP: 6 days (1-22 days) vs 3 days (1-7 days); p=0.01; log-rank analysis. In multivariate analysis, the two independent predictors of prolonged weaning were ICUAP [hazard ratio (HR): 2.4; 95% confidence interval (CI): 1.4-4.2] and chronic obstructive pulmonary disease (HR: 2.7; 95% CI: 1.6-4.5) CONCLUSIONS: ICU-acquired paresis is an independent predictor of prolonged weaning. Prevention of ICU-acquired neuromuscular abnormalities in patients recovering from severe acute illness should result in shorter weaning duration.

Aged↗
PubMed2004

Paresis following mechanical ventilation.

PURPOSE OF REVIEW: To review the medical literature on neuromuscular abnormalities acquired in the intensive care unit (ICU), particularly after mechanical ventilation, focusing on the most recent advances in this field. RECENT FINDING: Using a simple bedside muscle strength score, significant clinical weakness is detected in one fourth of patients awakening in ICU after more than 1 week of mechanical ventilation. Weakness is associated with a longer time on mechanical ventilation, although the exact relationship between limb and respiratory neuromuscular involvement remains unclear. Muscle involvement is often combined with axonal involvement and can predominate or occur in isolation in some patients. Although prolonged severe weakness is unusual, milder abnormalities may persist for several months after discharge. In addition to severity and duration of initial organ failures, both neuromuscular inactivity and use of corticosteroids make an independent contribution of the neuromuscular abnormalities. Conversely, strict glycemic control may prevent neuromuscular abnormalities, although this needs to be confirmed in general ICU patients. SUMMARY: Avoiding complete neuromuscular inactivity, using corticosteroids with greater discernment, and closely monitoring blood glucose levels might be worthwhile avenues for research in prevention of neuromuscular abnormalities acquired in the most severely ill ICU patients. Investigations of the severity of the respiratory neuromuscular involvement are also warranted.

Adrenal Cortex Hormones↗
PubMed2004

The neuropathology of septic shock.

The neuropathological correlates of encephalopathy and autonomic dysfunction in septic shock are unclear. We performed post mortem analysis of 5 brain areas susceptible to ischemia and 5 autonomic nuclei (AN) in 23 patients who had died in our intensive care unit (ICU) from septic shock and 8 dying from non-septic shock as well as 5 controls who had died suddenly from extracranial injury. Proinflammatory cytokine (IL1-beta and TNF-alpha) and inducible nitric oxide synthase (iNOS) expression was assessed by immunocytochemistry. Abnormalities in septic shock were: hemorrhages (26%), hypercoagulability syndrome (9%), micro-abscesses (9%), multifocal necrotizing leukoencephalopathy (9%) and ischemia (100%). The incidence of cerebral hemorrhage or hypercoagulability syndrome was not related to clotting disturbances. The intensity of ischemia within susceptible areas was the same in both ICU groups, but more pronounced in the autonomic centers of septic patients (P < 0.0001). Neuronal apoptosis assessed using anti-caspase 3 immunocytochemistry and in situ end labeling was more pronounced in the autonomic nuclei of septic patients. (P < 0.0001). TNF-alpha expression did not differ between groups but vascular iNOS expression assessed by immunocytochemistry was higher in sepsis (P<0.0001) and correlated with autonomic center neuronal apoptosis (P < 0.02). We conclude that septic shock is associated with diffuse cerebral damage and specific autonomic neuronal apoptosis which may be due to circulating factors particularly iNOS.

Adult↗
PubMed2004

Respiratory dysfunction in Guillain-Barré Syndrome.

Guillain-Barré Syndrome is the leading cause of nontraumatic acute paralysis in industrialized countries. About 30% of patients have respiratory failure requiring intensive care unit (ICU) admission and invasive mechanical ventilation. Progressive weakness of both the inspiratory and the expiratory muscles is the mechanism leading to respiratory failure. Aspiration pneumonia and atelectasis are common consequences of the bulbar muscle weakness and ineffective cough. The classical signs of respiratory distress occur too late to serve as guidelines for management, and measurements of vital capacity and static respiratory pressures are useful to determine the best times for starting and stopping mechanical ventilation. Several factors present at admission and during the ICU stay are known to predict a need for invasive mechanical ventilation. They include rapidly progressive motor weakness, involvement of both the peripheral limb and the axial muscles, ineffective cough, bulbar muscle weakness, and a rapid decrease in vital capacity. Specific treatments (plasma exchange and intravenous immunoglobulins) have decreased both the number of patients requiring ventilation and the duration of ventilation. The need for mechanical ventilation is associated with residual functional impairments, although all patients eventually recover normal respiratory muscle function.

Guillain-Barre Syndrome↗
PubMed2003

Apoptosis of neurons in cardiovascular autonomic centres triggered by inducible nitric oxide synthase after death from septic shock.

BACKGROUND: Results of experimental and clinical studies have shown that septic shock is associated with cardiovascular autonomic failure. Thus, we aimed to investigate the existence of ischaemia and apoptosis within the cerebral autonomic centres that control the cardiovascular system in patients with septic shock. METHODS: In a prospective cohort study, we did post-mortem examinations of supraoptic and paraventricular nuclei, cerebral amygdala, locus coeruleus, and medullary autonomic nuclei in 19 patients with septic shock, seven with non-septic shock and five who died suddenly from extracranial injury. Ischaemic and apoptotic neurons and microglial cells, and expression of tumour necrosis factor alpha (TNFalpha) and inducible nitric oxide synthase (iNOS) were scored. FINDINGS: Ischaemic, neuronal, and microglial apoptosis scores differed between groups (p=0.0007, p<0.0001, and p=0.0037, respectively) and were higher in patients with septic shock than in those with non-septic shock (p=0.0033, p=0.0005, and p=0.0235, respectively), and extra-cranial injury related deaths (p=0.0027, p=0.0007, and p=0.0045, respectively). There was little microglial activation and glial expression of TNFalpha. The scores for endothelial iNOS expression were different between the three groups (p<0.0001), and were higher in septic shock than in non-septic shock (p=0.0009) and than in extracranial injury related deaths (p=0.0007). Vascular expression of iNOS also correlated (Spearman tau=0.57) with autonomic-centre neuronal apoptosis in the combined septic and non-septic shock group. INTERPRETATION: Septic shock is associated with neuronal and glial apoptosis within the autonomic centres, which is strongly associated with endothelial iNOS expression.

Adult↗
PubMed2003

Transdiaphragmatic pressure control of airway pressure support in healthy subjects.

We designed a new servoventilator that proportionally adjusts airway pressure to transdiaphragmatic pressure (Pdi) generated by the subject during inspiration. Each cycle is triggered by either a preset Pdi increase or a preset inspiratory flow value (whichever is reached first), whereas cycling-off is flow-dependent. We evaluated the servoventilator in seven healthy subjects at normocapnia and three levels of hypercapnia (normocapnia + 3, + 6, and + 9 mm Hg) comparatively with spontaneous breathing. Triggering was by Pdi in six subjects and flow in one. At all end-tidal carbon dioxide pressure levels, time from onset of diaphragm electromyographic activity to inspiratory flow was similar with and without the servoventilator. Airway pressure increased proportionally to Pdi variation during servoventilator breathing. Flow, tidal volume, respiratory rate, intrinsic positive end-expiratory pressure, and esophageal and transdiaphragmatic pressure-time products increased significantly with hypercapnia with and without the servoventilator. Breathing pattern parameters were similar in the two breathing modes, and no differences were found for intrinsic positive end-expiratory pressure or gastric pressure variation during exhalation. Esophageal and transdiaphragmatic pressure-time products were lower with than without the servoventilator. The Pdi-driven servoventilator was well synchronized to the subjects effort, delivering a pressure proportional to Pdi and reducing respiratory effort at normocapnia and hypercapnia.

Adult↗