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Background: More and more, young children are victims of the ongoing epidemic of opioid use disorder. Xylazine, an alpha-2 adrenergic agonist with notorious use as a veterinary tranquilizer, is an increasingly encountered component of the illicit opioid supply in the US, but has been rarely documented in biological samples obtained from children. We report a 19-day-old infant with classic manifestations of central nervous system and respiratory depression associated with fentanyl and xylazine poisoning. Case report: A 19-day-old boy was taken to the emergency department (ED) by his parents for episodes of straining, breathholding, and his eyes rolling backwards. The formula-fed boy was born of an uncomplicated full-term spontaneous vaginal delivery and had previously been thriving. During ED triage assessment he had a period of apnea, then bradypnea, with pulse-oximetric oxygen saturation drop to 55%. He was supported with stimulation and supplemental oxygen via nonrebreather mask but remained lethargic, with temperature 96F, heart rate 166/min, and brisk capillary refill. Point of care blood dextrose testing was 88mg/dL. Analysis of respiratory secretions for common viruses by polymerase chain reaction was negative for respiratory syncytial virus, influenza, or SARS-CoV-2. Computed tomography imaging of the brain was unremarkable. A urine drug immunoassay (Vitros 4600 Chemistry , Ortho- Clinical Diagnostics) resulted positive for fentanyl (cutoff 1 ng/ mL), but negative for amphetamine, barbiturate, benzodiazepine, cannabinoids, cocaine, heroin, morphine, buprenorphine, methadone, or oxycodone. Liquid chromatography tandem mass spectroscopy analysis of the urine confirmed the presence of fentanyl (25 ng/mL) and norfentanyl (245 ng/mL). Gas chromatography with mass spectrometry also detected the presence of xylazine (qualitative result based on spectra matching). Over the ensuing hours the boy recovered fully and the family was connected with child protection services;an exposure route was not identified. Discussion(s): This 19-day-old infant suffered fentanyl/xylazine poisoning. The infant's age and urine fentanyl concentrations exclude pre-natal exposure as an explanation for the drug test findings, and the baby was bottle-fed excluding drug transmission through breast milk. Xylazine has been known to be in this hospital's regional heroin supply since the early 2000s, and in 2019 xylazine was implicated in more than 31% of opioid-associated deaths at the city's medical examiner's office. In 2022, many fentanyl samples tested by regional law enforcement find more xylazine than fentanyl. Until recently, xylazine was an uncommon finding in our testing of pediatric opioid poisoning victims. Similar to fentanyl, xylazine may cause pupillary miosis and CNS depression;unfortunately it may be resistant to reversal with naloxone. Conclusion(s): This case is remarkable for the young age of this infant ill from post-natal fentanyl poisoning and for the detection of xylazine in his urine. Healthcare providers may not immediately consider opioid poisoning in the differential diagnosis of infants with altered mental status, and proper toxicological testing is important for appropriate child protection support. Detection of xylazine is a marker for a non-medical, or "street," source of fentanyl.
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CASE: A 44 year old female with history of depression and recent suicide attempt presents with one week of cognitive and functional decline. One month prior to presentation, patient attempted suicide with opioids requiring intubation for respiratory depression and stroke sequelae. She was discharged from this stay after 12 days having returned to mental and functional baseline. Two weeks later, she demonstrated decreased focus and concentration, progressing to decreased mobility and akinesis, eventually presenting to our hospital. Admission metabolic and toxic workup was negative. CT head redemonstrated findings of previously known stroke. MRI demonstrated new increased T2 Flair of the parietal lobes and the cerebral white matter. LP was without evidence of infection or inflammation. Encephalitis panel and autoimmune workup were negative. Neurology consult suggested delayed post-hypoxic leukoencephalopathy as a possible diagnosis, given clinical course of improvement and subsequent decline, along with akinetic mutism and deep cortical white matter flair abnormalities. After failed trial of lorazepam, she was started on amantadine and her cognitive and functional status improved slowly. IMPACT/DISCUSSION: Delayed post-hypoxic leukoencephalopathy (DPHL) is a rare syndrome characterized by biphasic time course with initial recovery and subsequent cognitive and functional decline. DPHL can follow any event of prolonged cerebral hypoxia most frequently CO poisoning. It can occur with more common causes of hypoxia including overdose, cardiac arrest, and seizures;recent case reports have reported DPHL following severe covid infection. The clinical course involves a hypoxic event followed by a return to functional baseline typically lasting 7-21 days, after which progressive physical and mental decline occur. Signs include neuropsychiatric symptoms like amnesia and disorientation, as well as parkinsonism or akinetic mutism (1). The mechanism of DPHL is unclear. One possible mechanisms involves diffuse demyelination. The half life of myelin basic proteins is approximately 20 days, the length of the lucid interval. Hypoxia may abruptly halt the myelination process but symptoms may not emerge until a critical threshold of loss was achieved. Evaluation of DPHL involves considering other causes of encephalopathy, such as infection, substance use, stroke, catatonia, and toxins. In the absence of other causes, diagnosis of DPHL is based on characteristic time course following hypoxic event, symptoms, and MRI findings of diffuse T2 hyperintensity of cerebral white matter are pathognomonic (1). Treatment of DPHL is generally supportive. Limited evidence suggests amantadine may be of benefit. CONCLUSION: Physicians should consider DPHL in patients who have experienced cerebral hypoxia and present with the characteristic time course and imaging findings.
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Introduction: Conium maculatum, poison hemlock, is native to Europe, North Africa and Western Asia. Over the last 50 years, it has become more prevalent as an invasive species in the United States. Notorious for its role in Socrates' suicide in 399 BC and frequently referenced by Shakespeare, the plant has a rich history of toxicity in man. We present a case of an accidental hemlock exposure leading to acute interstitial pneumonia and acute respiratory distress syndrome. Case Presentation: A 58 year old male presented with acute dyspnea and cough with hemoptysis the morning after clearing wooded brush in his backyard. Other symptoms included tachycardia, diaphoresis, nausea, and diarrhea. His condition rapidly progressed to acute respiratory failure with imaging suggestive of ARDS. Thorough investigation for infectious and inflammatory etiology was unremarkable. Open lung biopsy was consistent with diffuse alveolar damage. Further history from the wife revealed the presence of significant amounts of poison hemlock identified in photos from the yard. Initial treatment included prednisone with prolonged taper with eventual transition to mycophenolate mofetil. After a prolonged hospital course, he was discharged with tracheostomy and continued ventilatory support. Discussion: Hemlock produces piperidine alkaloids akin to nicotine including coniine and γ-coniceine. These inhibit the nicotinic acetylcholine receptors of the central nervous system causing an array of symptoms that without intervention lead to respiratory depression and death. Diagnosis is based on history. Treatment is supportive, in many instances requiring mechanical ventilation. Conclusions: Even in the Covid era, ARDS differential diagnosis is dependent on thorough history taking, including obscure environmental exposures.
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Background: COVID-19 pandemic, limiting the availability of anesthesiologists, has impacted heavily on the organization of invasive cardiac procedures such as transcatheter atrial fibrillation (AF) ablation. Purpose: We compared the safety and efficacy of deep sedation with dexmedetomidine administered by electrophysiologists without anesthesiologist supervision, against the standard protocol performed with propofol. Methods: We retrospectively included all AF ablation procedures performed in 2020: 23 patients sedated with 1% propofol (2 ml bolus followed by infusion starting at 1 mg/Kg/h), 26 patients with dexmedetomidine (infusion starting at 0.7 mcg/Kg/h). Both groups additionally received 1 mcg/Kg of midazolam as a single bolus and 0.05 mg single boluses of fentanyl prior to ablation on each pair of pulmonary veins (PV). Primary outcomes were oxygen desaturation (< 90%) or need for assisted ventilation/intubation, bradycardia (heart rate < 45 bpm) and persistent hypotension (systolic blood pressure < 90 mmHg). Results: Baseline characteristics and hemodynamic variables did not differ between the two groups (all p > 0.05). In 8/23 (35%) patients propofol infusion velocity reduction was necessary to maintain the hemodynamic values, compared to 7/26 (27%) with dexmedetomidine. Inter-group comparison of hemodynamic variables during the procedure showed no statistically significant difference, despite a trend in favor of dexmedetomidine (3 respiratory depressions and 3 persistent hypotension episodes with propofol vs. 0 with dexmedetomidine;p = 0.057). Conclusion: Deep sedation with dexmedetomidine administered by electrophysiologists without anesthesiologist supervision is safe and effective for AF transcatheter ablation. A trend towards a lower incidence of hypotension and respiratory depression was noted when compared to propofol.
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Background: Chronic pain affects more than 100 million Americans, and opioids used for pain are 85-95% effective when administered for the right patient in the right dose at the right time. Conversions between opioids and routes of administration may be necessary due to pill burden, organ dysfunction, effectiveness, or insurance coverage. Although multiple opioid conversion tables exist, a universally accepted opioid analgesic conversion table does not. OhioHealth's Hospice and Palliative Medicine (HPM) teams utilize an HPM opioid conversion table, but consensus is not yet established. The goal of this study is to determine if there is consensus regarding the HPM opioid conversion table amongst the OhioHealth HPM pharmacists, physicians, and nurse practitioners. Methods: REDCap distributed a survey used to determine if there is consensus regarding the HPM opioid conversion table and to describe consensus differences between healthcare professionals. Data is summarized with means, standard deviations, medians, ranges, counts, and percentages. Consensus is achieved if the lower limit of the 95% confidence interval is greater than 70%. Secondary analyses are completed using descriptive statistics. Results: Forty-two of 53 HPM pharmacists (3), physicians (26), and nurse practitioners (15) responded to the survey. Consensus was reached for 60% (3) of the opioid conversion ratios surveyed. The majority of those surveyed (59.1%) reported utilizing the HPM conversion table with reasons being practice expectation (50%), ease of memorization (43.2%), evidence-based ratios (36.4%), and good clinical outcomes (43.2%). None of those surveyed reported an adverse effect attributed to the conversion ratios. Conclusion: Although consensus was not reached for two conversion ratios tested, consensus was reached for the remaining ratios. Notably, none of the HPM providers experienced an adverse effect, including respiratory depression, attributed to the conversion ratios. Reasons stated for not using the HPM conversion rations were unfamiliarity, difficulty understanding and/or using the ratios, and lack of evidence. Of the 11 respondents that did not use the HPM table, the majority reported 5 years or less of experience within hospice and palliative medicine. Additional education pertaining to evidence for the ratios and discussions regarding concerns may be necessary to reach consensus on all conversion ratios. Although the Delphi method may have been more appropriate to determine consensus, it was not feasible to execute it properly during the current coronavirus pandemic. A more standardized approach to opioid conversions could be established when there is consensus, with the goal of leading to minimization of adverse events resulting from under-and over-estimating opioid dose conversions.
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Objective: Acute exposure to hypoxia generally increase the ventilation. However, some of COVID-19 patients who suffer from pneumonia are characterized by hypoxic ventilatory depression with loss of dyspnea which is called as happy hypoxia. This report describes the background and the clinical issues of happy hypoxia. Methods: The mechanisms to increase ventilation and dyspnea under hypoxia are explained. Further, clinical issues and characteristics in COVID-19 are reviewed. Results: Genetic factors are definitely concerned with chemosensitivity to hypoxia. Further disease factors including COVID-19 infection could influence the attenuation of the chemosensitivity. This can be attributed to either ventilatory depression due to the modulation of metabolic substrate, adenosine in the brain, or autonomic neuropathy including the dysfunction of the carotid body. Conclusions: COVID-19 patients must be carefully treated and/or monitored to avoid hypoxic ventilator depression. The clinical application of aminophylline will be an issue to be considered.
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INTRODUCTION: Benzodiazepine (BZD)-based regimens are first-line therapy for alcohol withdrawal syndrome (AWS). Phenobarbital (PHB) is an alternative treatment but with limited guidance for use. We evaluated the efficacy and safety of PHB compared to BZD for AWS. METHODS: This was a single-center retrospective cohort study. Adult patients were included if they received BZD symptom-triggered protocol or PHB monotherapy for management of AWS and excluded if they received both therapies, were COVID positive, or died within 48 hours of hospital admission. Data collection started on December 31, 2020 and data were collected in reverse chronological order until target sample size was attained. Primary endpoint evaluated was development of AWS-related complications. Secondary endpoints included need for adjunct therapy, duration of mechanical ventilation, hospital and ICU length of stay (LOS), and hospital mortality. Safety endpoints included incidence of hypotension, bradycardia, and significant respiratory depression. RESULTS: 100 patients out of 164 screened patients were included, with 50 patients in PHB and 50 patients in BZD cohorts. Baseline characteristics were similar, except more patients in PHB cohort had history of alcohol dependence (82% vs. 56%, p< 0.001). Majority of BZD patients were in medical ICU while PHB patients were in surgical ICU. Baseline median MINDS scores were similar [PHB, 10 (5-16) vs. BZD, 11 (5-15), p=0.99]. Median (IQR) phenobarbital loading dose given was 14.8 (12.8-15.9) mg/kg followed by maintenance dose 356 (259-389) mg with a duration of 5 (3-5) days. Total lorazepam-equivalent dose given was 19.3 (5.0-44.0) mg with a duration of 4 (3-5) days. There was no significant difference in the primary endpoint [4 (8%) vs. 4(8%), p=1.00]. MINDS score post therapy initiation was significantly higher in BZD cohort [5 (1-14) vs. 15 (8-19), p< 0.001]. Patients who received PHB therapy had significantly shorter ICU LOS in days [3 (1-7) vs. 5 (2-6), p< 0.001] but no difference in hospital LOS [PHB, 8 (5-13) vs. BZD, 7 (5-12), p=0.37]. There were no significant differences in other secondary and safety endpoints. CONCLUSION: In this study there was no difference in efficacy or safety of PHB in management of AWS compared to BZD. Larger studies to confirm PHB as first-line AWS therapy are warranted.