Characteristics of victims of trauma requiring invasive mechanical ventilation with a short stay in critical care.

BACKGROUND: Many patients who are admitted to the intensive care unit (ICU) have needs which rapidly resolve and are discharged alive within 24 h. We sought to characterize the outcomes of critically ill trauma victims at our institution with a short stay in the ICU. METHODS: We conducted a retrospective cohort study of all critically ill adult trauma victims presenting to our ED between January 1st, 2011 and December 31st, 2019. We included patients who were endotracheally intubated in either the prehospital setting or the ED and were admitted either to the operating room (OR), angiography suite, or ICU. Our primary outcome was the proportion of patients who were discharged alive from the ICU within 24 h. RESULTS: We included 3869 patients meeting the criteria above who were alive at 24 h. This population was 78% male with a median age of 40 and 76% of patients suffered from blunt trauma. The median injury severity score (ISS) of the group was 21 [inter-quartile range (IQR) 11-30]. In-hospital mortality amongst the group was 12%. 17% of the group were discharged alive from the ICU within 24 h. Thirty-four percent of the group had an ISS ≤ 15. Of the group which left the ICU alive within 24 h, six patients (0.9%) died in the hospital, 2 % of patients were re-admitted to an ICU, and 0.6% of patients required re-intubation. CONCLUSIONS: We found that 17% of patients who were intubated in the prehospital setting or emergency department and subsequently hospitalized were discharged alive from the ICU within 24 h.

The Effect of Fluid Resuscitation Timing in Early Sepsis Resuscitation.

PURPOSE: The dose and timing of early fluid resuscitation in sepsis remains a debated topic. The objective of this study is to evaluate the effect of fluid timing in early sepsis management on mortality and other clinical outcomes. METHODS: Single-center, retrospective cohort study of emergency-department-treated adults (>18 years, n = 1032) presenting with severe sepsis or septic shock. Logistic regression evaluating the impact of 30 mL/kg crystalloids timing and mortality-versus-time plot controlling for mortality in emergency department sepsis score, lactate, antibiotic timing, obesity, sex, systemic inflammatory response syndrome criteria, hypotension, and heart and renal failures. This study is a subanalysis of a previously published investigation. RESULTS: Mortality was 17.1% (n = 176) overall and 20.4% (n = 133 of 653) among those in septic shock. 30 mL/kg was given to 16.9%, 32.2%, 16.2%, 14.5%, and 20.3% of patients within ≤1, 1 ≤ 3, 3 ≤ 6, 6 ≤ 24, and not reached within 24 h, respectively. A 24-h plot of adjusted mortality versus time did not reach significance, but within the first 12 h, the linear function showed a per-hour mortality increase (odds ratio [OR] 1.29, 95% confidence interval [CI] 1.02-1.67) which peaks around 5h, although the quadratic function does not reach significance (P = .09). When compared to patients receiving 30 mL/kg within 1 h, increased mortality was observed when not reached within 24 h (OR 2.69, 95% CI 1.37-5.37) but no difference when receiving this volume between 1 and 3 (OR 1.11, 95% CI 0.62-2.01), 3 and 6 (OR 1.83, 95% CI 0.97-3.52), or 6 and 24 h (OR 1.51, 95% CI 0.75-3.06). Receiving 30 mL/kg between 1 and 3 versus <1 h increased the incidence of delayed hypotension (OR 1.83, 95% CI 1.23-2.72) but did not impact need for intubation, intensive care unit admission, or vasopressors. CONCLUSIONS: We observed weak evidence that supports that earlier is better for survival when reaching fluid goals of 30 mL/kg, but benefits may wane at later time points. These findings should be viewed as hypothesis generating.

A Description of Mechanically Ventilated Patients Admitted From the Emergency Department With a Short Critical Care Stay.

BACKGROUND: Patients admitted to an intensive care unit (ICU) requiring invasive mechanical ventilation who are discharged alive from the ICU within 24 h are poorly characterized in the literature. OBJECTIVE: Our aim was to characterize a cohort of intubated emergency department (ED) patients who are extubated and discharged from the ICU within 24 h. METHODS: We conducted a retrospective, observational cohort study at a single level I trauma center from January 2017 to December 2019. We included adults who were admitted to an ICU from the ED requiring invasive mechanical ventilation. Our primary outcome was the proportion of patients who were discharged from the ICU alive within 24 h. RESULTS: Of 13,374 ED patients admitted to an ICU during the study period, 2871 patients were intubated and ventilated in the prehospital or ED settings. Of these, 14% were discharged alive from the ICU within 24 h of admission. Only 21% of these patients were intubated in the ED. We identified the following two distinct subpopulations comprising 62% of this short-stay group: patients with a primary discharge diagnosis of intoxication (47%) and minimally injured trauma patients (53%), with 4% of patients in both subgroups. CONCLUSIONS: A total of 14% of patients receiving intubation with mechanical ventilation in the prehospital environment or in the ED were discharged alive from the ICU within 24 h. We identified two distinct subgroups of patients with a short stay in intensive care who may be candidates for ED extubation, including patients with intoxication and minimally injured trauma patients.

A Retrospective Analysis of Guanfacine for the Pharmacological Management of Delirium.

Background Delirium is a syndrome of acute brain failure that represents a change from an individual's baseline cognitive functioning characterized by deficits in attention and multiple aspects of cognition that fluctuate in severity over time. The symptomatic management of delirium's behavioral manifestations remains difficult. The alpha-2 agonists, dexmedetomidine and clonidine, are efficacious, but their potential cardiovascular adverse effects limit their utilization. Guanfacine is an oral alpha-2 agonist with a lower potential for such adverse outcomes; however, its use in delirium has not been studied. Methods A retrospective descriptive analysis of guanfacine for managing hyperactive or mixed delirium at Tampa General Hospital from January 2020 to October 2020 was conducted. The primary outcome was the time reduction in acute sedative administration. Secondary outcomes included renewed participation in physical therapy or occupational therapy (PT/OT), decreased opioid use, and an incidence of cardiovascular adverse effects. Results One hundred forty-nine patients were identified as having received guanfacine for managing delirium during the study period. All experienced a reduction in acute sedative use after the initiation of guanfacine. In 93 patients receiving PT/OT and no longer participating due to behavioral agitation, 74% had a documented renewal of services within four days. Of 112 patients on opioids, 70% experienced a 25% reduction in opioid administration within four days. No patients experienced consecutive episodes of hypotension that required a change in their clinical care. Two patients experienced a single episode of consecutive bradycardia that led to the discontinuation of guanfacine.  Conclusions Based on our retrospective study, guanfacine is a well-tolerated medication for the management of delirium. Even in medically and critically ill patients, cardiovascular adverse events were rare with guanfacine. Patients treated with guanfacine experienced decreased acute sedative use for behavioral agitation. Additionally, patients treated with guanfacine received fewer opioids and were better able to participate in PT/OT. Future studies with prospective, randomized, placebo-controlled designs are warranted to evaluate this promising intervention for delirium further.

Anaesthesia for non-cardiac surgery in children and young adults with Fontan physiology.

INTRODUCTION: Patients with Fontan physiology require non-cardiac surgery. Our objectives were to characterise perioperative outcomes of patients with Fontan physiology undergoing non-cardiac surgery and to identify characteristics which predict discharge on the same day. MATERIALS AND METHOD: Children and young adults with Fontan physiology who underwent a non-cardiac surgery or an imaging study under anaesthesia between 2013 and 2019 at a single-centre academic children's hospital were reviewed in a retrospective observational study. Continuous variables were compared using the Wilcoxon rank sum test, and categorical variables were analysed using the Chi-square test or Fisher's exact test. Multivariable logistic regression analysis results are presented by adjusted odds ratios with 95% confidence intervals and p values. RESULTS: 182 patients underwent 344 non-cardiac procedures with anaesthesia. The median age was 11 years (IQR 5.2-18), 56.4% were male. General anaesthesia was administered in 289 (84%). 125 patients (36.3%) were discharged on the same day. On multivariable analysis, independent predictors that reduced the odds of same-day discharge included the chronic condition index (OR 0.91 per additional chronic condition, 95% CI 0.76-0.98, p = 0.022), undergoing a major surgical procedure (OR 0.17, 95% CI 0.05-0.64, p = 0.009), the use of intraoperative inotropes (OR 0.48, 95% CI 0.25-0.94, p = 0.031), and preoperative admission (OR = 0.24, 95% CI: 0.1-0.57, p = 0.001). DISCUSSION: In a contemporary cohort of paediatric and young adults with Fontan physiology, 36.3% were able to be discharged on the same day of their non-cardiac procedure. Well selected patients with Fontan physiology can undergo anaesthesia without complications and be discharged same day.

Psychosis After Infection With SARS-CoV-2 in an Adolescent: A Case Report.

As many as one-third of patients who have coronavirus disease 2019 (COVID-19) develop long-term neuropsychiatric symptoms, such as anxiety, depression, brain fog, psychosis, seizures, and suicidal behavior.1 Several case reports have demonstrated the association between psychotic symptoms following infection with COVID-19 in adults.1,2 In a first episode of psychosis, clinical findings on history, examination, and diagnostic studies may suggest that the psychotic symptoms are due to medical illness, which may be reversible. The presentation can include acute onset, predominance of visual or tactile hallucinations, and association with other neurological symptoms.3.

Anesthesia for pediatric rigid bronchoscopy and related airway surgery: Tips and tricks.

Bronchoscopy-guided diagnostic and interventional airway procedures are gaining in popularity and prominence in pediatric surgery. Many of these procedures have been used successfully in the adult population but have not been used in children due to a lack of appropriately sized instruments. Recent technological advances have led to the creation of instruments to enable many more diagnostic and therapeutic procedures to be done under bronchoscopic guidance. These procedures vary significantly in their length and invasiveness and require vastly different anesthetic plans that must be easily adapted to situational and procedural changes. In addition to close communication between the anesthesiology and procedural teams; an understanding of the type of procedure, anesthetic requirements, and potential patient risks is paramount to a successful anesthetic. This review will focus on new rigid bronchoscopic procedures, goals for their respective anesthetic management, and unique tips and trick for how to maintain adequate oxygenation and ventilation in each scenario.

Impact of Comorbid PTSD on Outcome of Repetitive Transcranial Magnetic Stimulation (TMS) for Veterans With Depression.

OBJECTIVE: A recent randomized controlled trial of repetitive transcranial magnetic stimulation (TMS) for major depressive disorder (MDD) in veterans raised the question of whether comorbid posttraumatic stress disorder (PTSD) negatively impacted the outcome of TMS in veterans. To address this, a quality database was analyzed to compare outcomes of MDD treated with TMS in veterans with and without comorbid PTSD. METHODS: The clinical outcomes of all consecutive veterans with MDD treated with TMS at the James A. Haley Veterans' Hospital as outpatients from October 2013 through September 2018 were included. Patients were initially evaluated by an experienced psychiatrist, and the diagnosis of MDD was made by clinical evaluation per DSM-IV-TR/DSM-5 criteria. At the start of treatment, after every 5 treatments, and at the end of treatment, patients were assessed with self-report and clinician-rated scales of depression. All data were abstracted from an existing quality database. RESULTS: Among the 118 patients treated with TMS for depression, 55 (47%) had comorbid PTSD and 63 (53%) had no comorbid PTSD. Response and remission rates by score on the Montgomery-Asberg Depression Rating Scale were similar between patients with PTSD (52.5% and 40.9%, respectively) and without PTSD (53.8% and 35.6%, respectively). No seizures or persistent adverse effects were observed or reported in either group. CONCLUSIONS: Comorbid PTSD did not impact the outcome of TMS for depression in this sample of veterans. Future studies should include formal ratings of PTSD to determine if the severity of PTSD affects the outcome.

Delirium Secondary to Lamotrigine Toxicity.

BACKGROUND: Lamotrigine is a phenyltriazine medication that has been approved by the United States Food and Drug Administration as monotherapy and as an adjunctive agent for the treatment of seizure disorder. It was later approved by the FDA for the treatment of bipolar disorder. Lamotrigine is generally well tolerated by patients, but some serious symptoms can occur during treatment. These severe side effects include rashes and multi-organ failure. Lamotrigine has also been associated with the development of mental status changes, frequently when used concurrently with other medications that may impact the metabolism of lamotrigine. OBJECTIVE: To present the case of a 65-year-old man being treated with lamotrigine and valproic acid who developed mental status changes after the addition of sertraline to his medication regimen, and to compare this case to existing cases reported in the literature. DISCUSSION: Our case adds to the existing literature by demonstrating that patients may experience adverse medication effects despite lamotrigine levels that are normally considered to be in the therapeutic range, highlighting the importance of clinical correlation when obtaining medication levels. CONCLUSION: Clinicians should use caution interpreting lamotrigine levels when working up delirium, as normal levels may not rule out the development of lamotrigine toxicity.

Adolescent Polypharmacy and Serotonin Syndrome.

OBJECTIVES: The objective of this study was to present a case and review serotonin syndrome and the risk of occurrence in children and adolescents on multiple psychotropic medications. METHODS: The clinical history of a patient in the University of South Florida's child and adolescent psychiatry clinic is presented. Literature review on serotonin syndrome, attention-deficit/hyperactivity disorder (ADHD), and psychostimulants was conducted through PubMed. RESULTS/DISCUSSION: We have presented a case of possible serotonin-related abnormal movements in an adolescent girl prescribed stimulants and multiple serotonergic medications. Serotonin syndrome may be precipitated through drug interactions that increase serum levels of psychotropic medications. Patients with ADHD often have comorbid psychiatric illness requiring treatment with medication. Amphetamine salts are an often-overlooked agent that potentiates serotonin through monoamine oxidase inhibitor (MAO) inhibition and neurotransmitter release. Children and adolescents on multiple psychotropic medications should be closely monitored for the triad of altered mental status, neuromuscular abnormalities, and autonomic hyperactivity. CONCLUSIONS: Patients with ADHD often have comorbid psychiatric illness and are treated with multiple psychotropic medications. Given the effects of drug-drug interactions and the serotonergic effects of psychostimulants, clinicians should remain vigilant for the triad of altered mental status, neuromuscular abnormalities, and autonomic hyperactivity seen in serotonin syndrome.

Assessment of nephrotoxicity associated with combined cisplatin and mitomycin C usage in laparoscopic hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) has been used to treat various peritoneal malignancies. Cisplatin and mitomycin C (MMC) are agents commonly used in these procedures and, individually, each has been associated with acute kidney injury (AKI). There is limited literature on the complications associated with the use of both agents in HIPEC. Therefore, we sought to determine the incidence of nephrotoxicity and electrolyte abnormalities in patients undergoing laparoscopic HIPEC using this chemotherapeutic combination. METHODS: We retrospectively evaluated patients undergoing laparoscopic HIPEC for gastric or gastroesophageal adenocarcinoma using both cisplatin and MMC. Sodium thiosulfate was given for renal protection and kidney function was evaluated daily up to postoperative day #2. Details regarding patient characteristics, selection criteria, chemotherapeutic regimen, perioperative lab values and anesthetic management were collected. RESULTS: Twenty-three patients underwent 31 laparoscopic HIPEC procedures. Fifteen (65%) were male and the median age was 57 (range 21-75). Thirteen procedures were associated with an elevation in creatinine (Cr) with the median difference between POD#2 and baseline being 0.09 mg/dL (range 0-0.43). The glomerular filtration rate median difference between POD#2 and baseline was -17 mL/min/1.37 sq. m (range -42 to 11). No cases demonstrated AKI, defined as a 50% increase in Cr levels above baseline. An 84% incidence of postoperative hypophosphatemia (26/31) and 94% incidence of postoperative hypocalcemia (29/31) was observed. CONCLUSION: The laparoscopic approach to HIPEC using both cisplatin and MMC in our cohort was not associated with an increased incidence of AKI. The incidence of hypophosphatemia and hypocalcemia needs further evaluation to determine the exact etiology. Precis' statement: We retrospectively studied the association of AKI with the combined use of cisplatin and MMC in laparoscopic HIPEC.

Incidence and Risk Factors for Perioperative Cardiovascular and Respiratory Adverse Events in Pediatric Patients With Congenital Heart Disease Undergoing Noncardiac Procedures.

BACKGROUND: While mortality and adverse perioperative events after noncardiac surgery in children with a broad range of congenital cardiac lesions have been investigated using large multiinstitutional databases, to date single-center studies addressing adverse outcomes in children with congenital heart disease (CHD) undergoing noncardiac surgery have only included small numbers of patients with significant heart disease. The primary objective of this study was to determine the incidences of perioperative cardiovascular and respiratory events in a large cohort of patients from a single institution with a broad range of congenital cardiac lesions undergoing noncardiac procedures and to determine risk factors for these events. METHODS: We identified 3010 CHD patients presenting for noncardiac procedures in our institution over a 5-year period. We collected demographic information, including procedure performed, cardiac diagnosis, ventricular function as assessed by echocardiogram within 6 months of the procedure, and classification of CHD into 3 groups (minor, major, or severe CHD) based on residual lesion burden and cardiovascular functional status. Characteristics related to conduct of anesthesia care were also collected. The primary outcome variables for our analysis were the incidences of intraoperative cardiovascular and respiratory events. Univariable and multivariable logistic regressions were used to determine risk factors for these 2 outcomes. RESULTS: The incidence of cardiovascular events was 11.5% and of respiratory events was 4.7%. Univariate analysis and multivariable analysis demonstrated that American Society of Anesthesiologists (≥3), emergency cases, major and severe CHD, single-ventricle physiology, ventricular dysfunction, orthopedic surgery, general surgery, neurosurgery, and pulmonary procedures were associated with perioperative cardiovascular events. Respiratory events were associated with American Society of Anesthesiologists (≥4) and otolaryngology, gastrointestinal, general surgery, and maxillofacial procedures. CONCLUSIONS: Intraoperative cardiovascular events and respiratory events in patients with CHD were relatively common. While cardiovascular events were highly associated with cardiovascular status, respiratory events were not associated with cardiovascular status.

Clinical repetitive transcranial magnetic stimulation for veterans with major depressive disorder.

BACKGROUND: Repetitive transcranial magnetic stimulation (TMS) is a relatively new treatment modality for patients with major depressive disorder (MDD). Numerous studies have demonstrated the efficacy of TMS for MDD in the general population. However, there is limited information regarding clinical outcomes among veterans receiving TMS for MDD. METHODS: The clinical outcome and characteristics of all veterans with MDD who were treated with TMS as outpatients at the James A. Haley Veterans' Hospital from October 2013 to December 2016 were assessed. RESULTS: Among 40 patients who received TMS, there was a significant improvement of depressive symptoms using the Quick Inventory of Depressive Symptomatology-Self-Report (45% response, 20% remission) and the Montgomery-Åsberg Depression Rating Scale (61.9% response, 42.9% remission). In addition to significant improvement in depressive symptoms, self-report of anxiety symptoms and function significantly improved. TMS was generally well tolerated, with only a small percentage of patients discontinuing treatment due to side effects. No seizures or persistent adverse effects were observed or reported. CONCLUSIONS: TMS is an effective and well-tolerated option for MDD in a veteran population with significant treatment resistance and multiple comorbidities.

Prevention of C5aR1 signaling delays microglial inflammatory polarization, favors clearance pathways and suppresses cognitive loss.

BACKGROUND: Pharmacologic inhibition of C5aR1, a receptor for the complement activation proinflammatory fragment, C5a, suppressed pathology and cognitive deficits in Alzheimer's disease (AD) mouse models. To validate that the effect of the antagonist was specifically via C5aR1 inhibition, mice lacking C5aR1 were generated and compared in behavior and pathology. In addition, since C5aR1 is primarily expressed on cells of the myeloid lineage, and only to a lesser extent on endothelial cells and neurons in brain, gene expression in microglia isolated from adult brain at multiple ages was compared across all genotypes. METHODS: C5aR1 knock out mice were crossed to the Arctic AD mouse model, and characterized for pathology and for behavior performance in a hippocampal dependent memory task. CX3CR1GFP and CCR2RFP reporter mice were bred to C5aR1 sufficient and knockout wild type and Arctic mice to enable sorting of microglia (GFP-positive, RFP-negative) isolated from adult brain at 2, 5, 7 and 10 months of age followed by RNA-seq analysis. RESULTS: A lack of C5aR1 prevented behavior deficits at 10 months, although amyloid plaque load was not altered. Immunohistochemical analysis showed no CCR2+ monocytes/macrophages near the plaques in the Arctic brain with or without C5aR1. Microglia were sorted from infiltrating monocytes (GFP and RFP-positive) for transcriptome analysis. RNA-seq analysis identified inflammation related genes as differentially expressed, with increased expression in the Arctic mice relative to wild type and decreased expression in the Arctic/C5aR1KO relative to Arctic. In addition, phagosomal-lysosomal gene expression was increased in the Arctic mice relative to wild type but further increased in the Arctic/C5aR1KO mice. A decrease in neuronal complexity was seen in hippocampus of 10 month old Arctic mice at the time that correlates with the behavior deficit, both of which were rescued in the Arctic/C5aR1KO. CONCLUSIONS: These data are consistent with microglial polarization in the absence of C5aR1 signaling reflecting decreased induction of inflammatory genes and enhancement of degradation/clearance pathways, which is accompanied by preservation of CA1 neuronal complexity and hippocampal dependent cognitive function. These results provide links between microglial responses and loss of cognitive performance and, combined with the previous pharmacological approach to inhibit C5aR1 signaling, support the potential of this receptor as a novel therapeutic target for AD in humans.

Cell-specific deletion of C1qa identifies microglia as the dominant source of C1q in mouse brain.

BACKGROUND: The complement cascade not only provides protection from infection but can also mediate destructive inflammation. Complement is also involved in elimination of neuronal synapses which is essential for proper development, but can be detrimental during aging and disease. C1q, required for several of these complement-mediated activities, is present in the neuropil, microglia, and a subset of interneurons in the brain. METHODS: To identify the source(s) of C1q in the brain, the C1qa gene was selectively inactivated in the microglia or Thy-1+ neurons in both wild type mice and a mouse model of Alzheimer's disease (AD), and C1q synthesis assessed by immunohistochemistry, QPCR, and western blot analysis. RESULTS: While C1q expression in the brain was unaffected after inactivation of C1qa in Thy-1+ neurons, the brains of C1qa FL/FL :Cx3cr1 CreERT2 mice in which C1qa was ablated in microglia were devoid of C1q with the exception of limited C1q in subsets of interneurons. Surprisingly, this loss of C1q occurred even in the absence of tamoxifen by 1 month of age, demonstrating that Cre activity is tamoxifen-independent in microglia in Cx3cr1 CreERT2/WganJ mice. C1q expression in C1qa FL/FL : Cx3cr1 CreERT2/WganJ mice continued to decline and remained almost completely absent through aging and in AD model mice. No difference in C1q was detected in the liver or kidney from C1qa FL/FL : Cx3cr1 CreERT2/WganJ mice relative to controls, and C1qa FL/FL : Cx3cr1 CreERT2/WganJ mice had minimal, if any, reduction in plasma C1q. CONCLUSIONS: Thus, microglia, but not neurons or peripheral sources, are the dominant source of C1q in the brain. While demonstrating that the Cx3cr1 CreERT2/WganJ deleter cannot be used for adult-induced deletion of genes in microglia, the model described here enables further investigation of physiological roles of C1q in the brain and identification of therapeutic targets for the selective control of complement-mediated activities contributing to neurodegenerative disorders.