Sarah Murphy

An international study of the performance of sample collection from patients

Background and Objectives Collection of a blood sample from the correct patient is the first step in the process of safe transfusion. The aim of this international collaborative study was to assess the frequency of mislabelled and miscollected samples drawn for blood grouping.

Intracranial Hemorrhage: Mechanisms of Secondary Brain Injury

ICH is a disease with high rates of mortality and morbidity, with a substantial public health impact. Spontaneous ICH (sICH) has been extensively studied, and a large body of data has been accumulated on its pathophysiology. However, the literature on traumatic ICH (tICH) is limited, and further investigations of this important topic are needed. This review will highlight some of the cellular pathways in ICH with an emphasis on the mechanisms of secondary injury due to heme toxicity and to events in the coagulation process that are common to both sICH and tICH.

Delirium in Critically Ill Children: An International Point Prevalence Study*

Objectives: To determine prevalence of delirium in critically ill children and explore associated risk factors. Design: Multi-institutional point prevalence study. Setting: Twenty-five pediatric critical care units in the United States, the Netherlands, New Zealand, Australia, and Saudi Arabia. Patients: All children admitted to the pediatric critical care units on designated study days (n = 994). Intervention: Children were screened for delirium using the Cornell Assessment of Pediatric Delirium by the bedside nurse. Demographic and treatment-related variables were collected. Measurements and Main Results: Primary study outcome measure was prevalence of delirium. In 159 children, a final determination of mental status could not be ascertained. Of the 835 remaining subjects, 25% screened positive for delirium, 13% were classified as comatose, and 62% were delirium-free and coma-free. Delirium prevalence rates varied significantly with reason for ICU admission, with highest delirium rates found in children admitted with an infectious or inflammatory disorder. For children who were in the PICU for 6 or more days, delirium prevalence rate was 38%. In a multivariate model, risk factors independently associated with development of delirium included age less than 2 years, mechanical ventilation, benzodiazepines, narcotics, use of physical restraints, and exposure to vasopressors and antiepileptics. Conclusions: Delirium is a prevalent complication of critical illness in children, with identifiable risk factors. Further multi-institutional, longitudinal studies are required to investigate effect of delirium on long-term outcomes and possible preventive and treatment measures. Universal delirium screening is practical and can be implemented in pediatric critical care units.

Pediatric Neurocritical Care

Pediatric neurocritical care is an emerging multidisciplinary field of medicine and a new frontier in pediatric critical care and pediatric neurology. Central to pediatric neurocritical care is the goal of improving outcomes in critically ill pediatric patients with neurological illness or injury and limiting secondary brain injury through optimal critical care delivery and the support of brain function. There is a pressing need for evidence based guidelines in pediatric neurocritical care, notably in pediatric traumatic brain injury and pediatric stroke. These diseases have distinct clinical and pathophysiological features that distinguish them from their adult counterparts and prevent the direct translation of the adult experience to pediatric patients. Increased attention is also being paid to the broader application of neuromonitoring and neuroprotective strategies in the pediatric intensive care unit, in both primary neurological and primary non-neurological disease states. Although much can be learned from the adult experience, there are important differences in the critically ill pediatric population and in the circumstances that surround the emergence of neurocritical care in pediatrics.

Ultrasound findings in Plasmodium falciparum malaria: a pilot study.

Objective: To investigate whether hand-carried ultrasound technology may be valuable in the assessment of children with acute malaria. Every year, approximately 800,000 children under the age of 5 yrs die of complications of Plasmodium falciparum malaria infection. The advent of hand-carried ultrasound technology has made diagnostic ultrasonography possible in underresourced settings. Design: We performed a pilot observational study collecting clinical data and performing ultrasound examinations on children diagnosed with P. falciparum malaria infection. The targeted ultrasound examination included measurement of optic nerve sheath diameter, color transcranial Doppler insonation of the cerebral vasculature, cardiac ultrasound, and abdominal ultrasound. Setting: Pediatric acute care unit of Mulago Hospital in Kampala, Uganda. Patients: Thirty-three hospitalized children between the ages of 6 months and 12 yrs with documented acute P. falciparum infection. Intervention: Targeted bedside ultrasound examination. Measurements and Main Results: Increased optic nerve sheath diameter was observed in one third of all patients with malaria and in 100% of the patients diagnosed with cerebral malaria. Although higher-than-normal cerebral blood flow velocities were demonstrated in three (25%) of 12 patients with severe anemia, most patients demonstrated a normal cerebral blood flow velocity, suggesting a blunted response to anemia. We did not find evidence of pulmonary hypertension by cardiac ultrasound, and cardiac function did not seem depressed, even among patients with severe anemia and lactic acidosis. Finally, spleen size as determined by palpation significantly overestimated the true incidence of splenomegaly as measured by ultrasound (48% and 24%, respectively). Conclusions: A targeted ultrasound examination focusing on optic nerve sheath diameter, color transcranial Doppler, cardiac ultrasound, and spleen size may prove useful for patient classification, risk stratification, research studies, and treatment monitoring in pediatric malaria. More studies should be done.

Bedside Monitoring of Vascular Mechanisms in CNS Trauma: The Use of Near-Infrared Spectroscopy (NIRS) and Transcranial Doppler (TCD)

Ischemia and adequacy of regional and global cerebral blood flow are important determinants of outcome in traumatic brain injury (TBI). Although brain ischemia may be a major common pathway of secondary brain damage following TBI, hyperemia and reperfusion injury may also occur and lead to elevated intracranial pressure and decreased cerebral perfusion pressure. Bedside monitors of cerebral ischemia include near-infrared spectroscopy (NIRS), transcranial Doppler ultrasound (TCD), continuous electroencephalography, and brain tissue microdialysis. This chapter will describe how NIRS and TCD enhance our understanding of vascular pathology following a brain injury and their potential applications in the acute management of TBI.

Diffuse cutaneous mastocytosis with novel somatic KIT mutation K509I and association with tuberous sclerosis

Diffuse cutaneous mastocytosis (DCM) is a rare but potentially fatal condition when diagnosis and targeted treatments are delayed. This case illustrates the life‐threatening complications in DCM and reviews the currently available treatments. To our knowledge, this is the first report of mastocytosis with somatic K509I mutation and concomitant tuberous sclerosis.

Molecular Biology of Brain Injury: 2012

Here we will cover a number of topics relevant to the molecular biology of acute brain injury beginning with an introduction to basic neurotransmitter systems and function, including excitatory (glutamate, acetylcholine, others) and inhibitory (GABA, glycine) neurotransmitters. To illustrate how these systems can interact with systemic processes we describe the cholinergic anti-inflammatory response, one way that the brain communicates with the peripheral immune system to downregulate an inflammatory response. Glutamate receptor physiology is introduced and the concept of excitotoxicity, central to all forms of acute central nervous system injury, is explained including the roles of metabotropic and ionotropic signaling. This leads to analysis of modes and mechanisms of programmed cell death after acute brain injury with an emphasis on programmed necrosis, apoptosis, caspases, poly-ADP-ribose polymerase, mitochondrial permeability transition, and oxidative stress, including coverage of the new field of oxidative lipidomics, which has provided a link between reactive oxygen species generation, release of mitochondrial cytochrome C, and cell death via specific oxidation of cardiolipin after acute brain and cellular injury. Links between oxidative and nitrosative stress and neuroinflammation and how these fundamental processes relate to brain injury are also included. Finally, extracellular matrix proteases, including matrix metalloproteinases and tissue plasminogen activator and their role in neurodegeneration and neuroprotection, as stroke biomarkers, and as mediators of blood–brain barrier damage are elucidated.

Managing Edema and Intracranial Pressure in the Intensive Care Unit

Despite several decades of intensive research efforts in the laboratory and the clinic, treatment for traumatic brain injury remains supportive and directed towards controlling intracranial pressure (ICP). First-line therapies for ICP control include positioning to promote jugular venous drainage, sedation and muscle relaxation, modest hyperventilation, and hyperosmolar therapy. Second-line therapies include barbiturate coma, systemic hypothermia, and decompressive craniectomy. Although all of these therapies can be used to treat intracranial hypertension, none have been shown to improve outcome in patients with TBI. This chapter reviews the current therapies used for ICP control with an emphasis on children with TBI.