Marek A. Mirski

Ventilator-associated pneumonia in the ICU

Ventilator-associated pneumonia (VAP) is defined as pneumonia that occurs 48–72 hours or thereafter following endotracheal intubation, characterized by the presence of a new or progressive infiltrate, signs of systemic infection (fever, altered white blood cell count), changes in sputum characteristics, and detection of a causative agent [1]. VAP contributes to approximately half of all cases of hospital-acquired pneumonia [1, 2]. VAP is estimated to occur in 9–27 % of all mechanically ventilated patients, with the highest risk being early in the course of hospitalization [1, 3]. It is the second most common nosocomial infection in the intensive care unit (ICU) and the most common in mechanically ventilated patients [4, 5]. VAP rates range from 1.2 to 8.5 per 1,000 ventilator days and are reliant on the definition used for diagnosis [6]. Risk for VAP is greatest during the first 5 days of mechanical ventilation (3 %) with the mean duration between intubation and development of VAP being 3.3 days [1, 7]. This risk declines to 2 %/day between days 5 to 10 of ventilation, and 1 %/day thereafter [1, 8]. Earlier studies placed the attributable mortality for VAP at between 33–50 %, but this rate is variable and relies heavily on the underlying medical illness [1]. Over the years, the attributable risk of death has decreased and is more recently estimated at 9–13 % [9, 10], largely because of implementation of preventive strategies. Approximately 50 % of all antibiotics administered in ICUs are for treatment of VAP [2, 4]. Early onset VAP is defined as pneumonia that occurs within 4 days and this is usually attributed to antibiotic sensitive pathogens whereas late onset VAP is more likely caused by multidrug resistant (MDR) bacteria and emerges after 4 days of intubation [1, 4]. Thus, VAP poses grave implications in endotracheally intubated adult patients in ICUs worldwide and leads to increased adverse outcomes and healthcare costs. Independent risk factors for development of VAP are male sex, admission for trauma and intermediate underlying disease severity, with odds ratios (OR) of 1.58, 1.75 and 1.47–1.70, respectively [7].

Deep brain stimulation of the anterior nucleus of the thalamus: Effects of electrical stimulation on pilocarpine-induced seizures and status epilepticus

PURPOSEnElectrical stimulation of the anterior nucleus of the thalamus appears to be effective against seizures in animals and humans. As the optimal stimulation settings remain elusive, we studied the effects of different stimulation parameters against pilocarpine induced seizures and status epilepticus (SE).nnnMETHODSnAdult rats had electrodes implanted bilaterally into the AN. Five days later, different groups of animals were stimulated with 1000 microA, 500 microA, or 200 microA and frequencies of either 20 Hz or 130 Hz. Pilocarpine (350 mg/kg i.p.) was injected 5 min after stimulation onset and seizures were monitored. Sham-treated controls had electrodes implanted but did not receive stimulation until they developed SE. After SE, these animals had the electrodes turned on to assess whether AN stimulation could arrest ongoing ictal activity.nnnRESULTSnCompared to sham-treated controls (n=8), stimulation at 500 microA (n=13) significantly increased the latency for seizures and SE by 1.9-2.2-fold. In contrast, stimulation at 1000 microA (n=8) produced a non-significant decrease in the latencies to these events. No major effect was observed with stimulation at 200 microA (n=11). Similar results were obtained for each current intensity, regardless of the stimulation frequency used (20 Hz and 130 Hz). In sham-treated controls that had the electrodes turned on after SE, stimulation was not able to arrest ongoing ictal activity.nnnCONCLUSIONSnThe anticonvulsant effects of AN stimulation against pilocarpine-induced seizures were mainly determined by the current and not the frequency of stimulation. AN stimulation initiated after SE onset was ineffective.

Spectral analysis of a thalamus-to-cortex seizure pathway

Physiological evidence has shown that the anterior thalamus (AN) and its associated efferents/afferents constitute an important propagation pathway for one animal model of generalized tonic clonic epileptic seizures. In this study the authors extend and confirm the support for ANs role by examining neuro-electric signal indicators during seizure episodes. They show that the electroencephalogram (EEG) recorded from AN is highly coherent with the EEG derived from the cortex (CTX). By removing the effects of another thalamic nucleus, posterior thalamus (PT)-unaffiliated with the tract linking AN to cortex-partial coherence analysis leaves the CTX/AN coherence undiminished. The most robust band of strong CTX-AN coherence is centered around the spike wave pacing frequency of 1-3 Hz. Partial-multiple coherence analysis techniques are used to remove the possible signal contributions from hippocampus in addition to PT. The CTX-AN coherence still remains undiminished in the low-frequency bands. Conclusive evidence from coherence studies and other spectral measures reaffirm the special role of the AN in the propagation of seizure activity from subcortex to cortex.

Intensive care of aneurysmal subarachnoid hemorrhage: an international survey

BackgroundPatients with aneurysmal subarachnoid hemorrhage (SAH) are routinely admitted to the intensive care unit for the management of neurological and systemic complications.ObjectiveTo determine the clinical practices of intensive care physicians treating SAH, and to evaluate the relationship between these practices and published evidence.DesignSurvey.ParticipantsPhysicians identified through the Society of Critical Care Medicine (SCCM), the European Society of Intensive Care Medicine (ESICM), and the Neurocritical Care Society (NCS).InterventionsThe research team classified published clinical research on key interventions in SAH diagnosis and therapy, and then generated a 45-item online questionnaire which was distributed to SCCM, NCS, and ESICM members.ResultsThere were 626 completed surveys, 51% from the USA or Canada, 35% from Europe, and 14% from other regions. Respondents included anesthesiologists (38%), internists (29%), neurologists (14%), and neurosurgeons (8%). Agreement with selected evidence-based recommendations was variable (39–92%) and did not depend on the quality of the supporting data. Significant practice differences were noted between respondents from North America and Europe, and between those working in high and low-volume centers (respectively >40 and ≤40 SAH cases per year).ConclusionsThis study demonstrates that the practices of intensive care physicians treating SAH are heterogeneous and often at variance with available evidence.

Reduction of complication rate in percutaneous dilation tracheostomies.

Introduction: Percutaneous dilation tracheotomy (PDT) is now an accepted alternative to surgical tracheotomy in certain patients. We began performing these procedures in 2000 and use it regularly in select intensive care unit patients requiring prolonged intubation and mechanical ventilation.

Percutaneous dilation tracheotomy in intensive care unit patients.

Objectives In our department, we routinely use percutaneous dilation tracheotomy (PDT) in select intensive care unit (ICU) patients requiring prolonged intubation and mechanical ventilation. We present our experience with this technique and discuss the pros and cons of PDT in the intensive care setting. Study Design and Setting We conducted a retrospective study of consecutive PDTs performed in our institution between 2002 and 2004. Demographic information and procedural and postoperative complications were noted. Results Two hundred seventy-four PDTs were performed on intensive care unit patients during this time period. Complications included five cases of excessive intraoperative bleeding (1.8%), one postoperative hemorrhage (0.3%), one tracheoesophageal fistula (0.3%), one pneumothorax (0.3%), and four accidental decannulations (1.4%). No PDT-associated deaths occurred. Conclusions PDT is advantageous for the patient as it is performed at bedside in the ICU. It is our conclusion that this technique is suitable for many, but not all, critical care patients.

Anticonvulsant serotonergic and deep brain stimulation in anterior thalamus

OBJECTIVEnAnterior thalamus (AN) has been shown to mediate seizures in both focal and generalized models. Specific regional increase in AN serotonergic activity was observed following AN-DBS in our pentylenetetrazol (PTZ) rodent model of acute seizures, and this increase may inhibit seizures and contribute to the mechanism of anticonvulsant DBS.nnnMETHODSnAnesthetized rats with AN-directed dialysis cannula with scalp/depth EEG were infused with PTZ at 5.5mg/(kg min) until an EEG seizure occurred. Eight experimental groups of AN-dialysis infusion were evaluated: controls (dialysate-only), 10 and 100 microM serotonin 5-HT(7) agonist 5-carboxamidotryptamine (5-CT), 1, 10 and 100 microM serotonin antagonist methysergide (METH), AN-DBS, and 100 microM METH+AN-DBS.nnnRESULTSnLatency for seizures in control animals was 3,120+/-770 s (S.D.); AN-DBS delayed onset to 5018+/-1100 (p<0.01). AN-directed 5-CT increased latency in dose-dependent fashion: 3890+/-430 and 4247+/-528 (p<0.05). Methysergide had an unexpected protective effect at low-dose (3908+/-550, p<0.05) but not at 100 microM (2687+/-1079). The anticonvulsant action of AN-DBS was blocked by prior dialysis using 100 microM METH. Surface EEG burst count and nonlinear analysis (H-Statistic) noted significant (p<0.05) increased pre-ictal epileptiform bursts in 5-CT, methysergide, but not DBS group compared to control.nnnCONCLUSIONnIncreased serotonergic activity in AN raised PTZ seizure threshold, similar to DBS, but without preventing cortical bursting. 5-Carboxamidotryptamine, a 5-HT(7) agonist, demonstrated dose-dependent seizure inhibition. Methysergide proved to have an inverse, dose-dependent agonist property, antagonizing the action of AN-DBS at the highest dose. Anticonvulsant AN-DBS may in part act to selectively alter serotonin neurotransmission to raise seizure threshold.

Neurologic injury and mechanical ventilation

Mechanical ventilation in neurologically injured patients presents a number of unique challenges. Patients who are intubated due to a primary neurologic injury often experience respiratory phenomena secondary to that injury, including elevation of intracranial pressure (ICP) in response to mechanical ventilation and variations in respiratory patterns. These problems often require unique ventilator strategies that are designed to minimize the impact of the ventilator on ICP and brain oxygenation. Balancing the need to maintain brain oxygenation and control of ICP can be complicated by the effects of ventilator management on ICP. We will examine the consequences of ventilator management as they relate to parameters that affect ICP and brain oxygenation in patients who have neurologic injury.

The Role of Neurocritical Care: A Brief Report on the Survey Results of Neurosciences and Critical Care Specialists

BackgroundNeurocritical care is a new subspecialty field in medicine that intersects with many of the neuroscience and critical care specialties, and continues to evolve in its scope of practice and practitioners. The objective of this study was to assess the perceived need for and roles of neurocritical care intensivists and neurointensive care units among physicians involved with intensive care and the neurosciences.MethodsAn online survey of physicians practicing critical care medicine, and neurology was performed during the 2008 Leapfrog initiative to formally recognize neurocritical care training.ResultsThe survey closed in July 2009 and achieved a 13% response rate (980/7524 physicians surveyed). Survey respondents (mostly from North America) included 362 (41.4%) neurologists, 164 (18.8%) internists, 104 (11.9%) pediatric intensivists, 82 (9.4%) anesthesiologists, and 162 (18.5%) from other specialties. Over 70% of respondents reported that the availability of neurocritical care units staffed with neurointensivists would improve the quality of care of critically ill neurological/neurosurgical patients. Neurologists were reported as the most appropriate specialty for training in neurointensive care by 53.3%, and 57% of respondents responded positively that neurology residency programs should offer a separate training track for those interested in neurocritical care.ConclusionBroad level of support exists among the survey respondents (mostly neurologists and intensivists) for the establishment of neurological critical care units. Since neurology remains the predominant career path from which to draw neurointensivists, there may be a role for more comprehensive neurointensive care training within neurology residencies or an alternative training track for interested residents.

Sinusoidal Modeling of Ictal Activity Along a Thalamus-to-Cortex Seizure Pathway I: New Coherence Approaches

Understanding associations in neuronal circuitry is critical for tracing epilepsy pathways. Two new methods of measuring coherence between field potentials and EEG channels are proposed for modeling the level of linear association between channels during epileptic seizures. These methods rely upon modeling the repetitive clonic seizure activity as a sum of sinusoids with varying degrees of phase locking. Estimating the amplitude of sinusoids from correlation and cross-correlation time domain data, we can find the coherences from a ratio of these amplitudes. One method utilizes amplitude finding from the multiple signal classification (MUSIC) technique. The other method uses alterations in amplitude of individual sinusoids and their ratios in a matrix pencil equation formed from cross- and auto-correlation matrices. The corresponding generalized eigenvalues of these equations form the coherence ratios. This utilizes the estimation of signal parameters using rotational invariance techniques (ESPRIT) algorithm to arrive at coherence amplitude ratios. Simulations illustrate that the MUSIC method provides better noise immunity as it outperforms the conventional Fourier transform-based method for coherence estimation. Both coherence estimators reflect presence of sinusoidal components that are propagated or not propagated along a particular transmission pathway. We illustrate the value of both methods by examining the strength of correlation between seizure EEG from specific thalamic nuclei and cortex in a rodent model of generalized epilepsy. The pentylenetetrazol (PTZ) chemoconvulsant model in rats reflects selective activation of the anterior thalamic nucleus. Using both methods, this neuronal element has much larger coherence with cortex than another thalamic region, the posterior thalamus (p < 0.05). These methods isolate the unique contribution of anterior thalamus in the formation of an ictal network and corroborate earlier conventional or periodogram techniques.