Drowning incidents precipitated by unusual causes (DIPUCs): A narrative review of their diagnoses, evaluation and management.

Drowning is a cause of significant morbidity and mortality worldwide. In most circumstances, the proximate cause is attributable to human factors, such as inexperience, fatigue, intoxication, or hazardous water conditions. The phenomenon of drowning incidents precipitated by unusual circumstances (DIPUCs) - either fatal or nonfatal - involving otherwise healthy individuals under generally safe conditions has not been comprehensively addressed in the medical and drowning literature to date. In this review, we discuss etiologies of DIPUCs, diagnostic clues, suggested workup, suggested postmortem testing, and implications for surviving patients and families. Identifying the cause of a drowning incident can be extremely challenging for the initially treating physician, relying perforce on historical context, environmental clues, physical exam, medical history, eyewitness accounts or video recordings. If no clear explanation for a drowning incident emerges despite a thorough investigation, clinicians should consider some of the less common diagnoses we describe in this paper, and, when appropriate, refer for an autopsy with postmortem molecular genetic testing. While time-consuming, these efforts can prove life-saving for some non-fatal drowning victims and the families of all victims of DIPUCs.

Epinephrine in Cardiac Arrest: Identifying a Potential Limit for Resuscitation.

Introduction: Epinephrine continues to be a fundamental part of the Advanced Cardiac Life Support algorithm despite a lack of evidence that it improves neurologically intact survival. Our aim was both to identify a potential upper limit of epinephrine use in resuscitations and to demonstrate real-world epinephrine use in different patient subgroups. Methods: This was a single-center, retrospective cohort study, conducted between August 1, 2016-July 1, 2021, of patients with medical cardiac arrest who were administered a known number of epinephrine doses. The primary outcome was neurologically intact discharge defined by a modified Rankin scale ≤3, with secondary outcomes of comparing epinephrine doses by age, rhythm, and emergency medical services vs emergency department administration of epinephrine. Results: The study included 1,330 patients, with 184 patients (13.8%) surviving to neurologically intact discharge. The primary outcome of neurologically intact discharge was found in 89 (65.4%) patients in the zero epinephrine dose group, 75 (20.0%) in the 1-3 dose group, 15 (4.3%) in the 4-6 dose group, and one (0.002%) in the ≥7 dose group (P < 0.001). Patients received similar amounts of epinephrine when stratified by age, while patients with shockable rhythms received more epinephrine than patients with non-shockable rhythms. Conclusion: There was a significant decrease in neurologically intact discharge with increasing number of epinephrine doses, and our data suggests that seven or more doses of epinephrine is almost always futile. While further prospective studies are needed, clinicians should consider epinephrine doses when weighing the futility or benefit of continued resuscitation efforts.

Serotonin syndrome from sertraline monotherapy.

Serotonin syndrome (SS) is a rare, potentially life-threatening adverse drug reaction. Selective serotonin reuptake inhibitors (SSRIs) are among a number of pharmaceuticals that all contribute to SS, but SS caused by SSRI monotherapy is rare. We present a case of probable sertraline-induced SS. A 36-year-old male presented to the emergency department four times in one week with a constellation of autonomic and neuromuscular symptoms. He had been taking sertraline at a therapeutic dose for less than three months. Moderate SS was diagnosed using the Hunter criteria during the fourth visit, when it was seen that he had hyperreflexia and inducible ankle clonus. The patient's symptoms resolved within 24 hours with lorazepam, intravenous fluids, and discontinuation of sertraline. In the emergency department it is important to have a high clinical suspicion for SS even if the patient is taking SSRI monotherapy at therapeutic doses.

Joint replacement in X-linked hypophosphatemia.

X-linked hypophosphatemia (XLH) is associated with a pervasive, severe degenerative osteoarthritis. We conducted a retrospective chart review/patient survey using the Knee or Hip Osteoarthritis Outcome Score Physical Function Short Form. Fourteen total knee arthroplasties and 7 total hip arthroplasties among 11 patients were included. The mean KOOS-PS score was 31.4 ±â€¯9.7 with a mean follow up of 6.9 years. Mean HOOS-PS score was 14.8 ±â€¯12.9 at a mean follow up of 7.6 years. One knee failed due to aseptic loosening and one hip was revised due to polyethylene wear. In conclusion, total joint arthroplasty is beneficial in XLH.

Tourniquet use in the prehospital setting: Are they being used appropriately?

OBJECTIVE: The objective of this study was to evaluate tourniquet use in the Hartford prehospital setting during a 34-month period after the Hartford Consensus was published, which encouraged increasing tourniquet use in light of military research. DESIGN: This was a retrospective review of patients with bleeding from a serious extremity injury to determine appropriateness of tourniquet use or omission. SETTING: Level II trauma center between April 2014 and January 2017. PARTICIPANTS: Eighty-four patients met inclusion criteria and were stratified based on tourniquet use during prehospital care. MAIN OUTCOME MEASURES: Five of the 84 patients received a tourniquet. All five of those tourniquets (100 percent of the group, 6.0 percent of the population) were not indicated and deemed inappropriate. Three of the 84 patients did not receive a tourniquet when one was indicated (3.8 percent of the group, 3.6 percent of the population) and these omissions were also deemed inappropriate. Total error rate was 9.5 percent (8/84). RESULTS: There was a significant association between Mangled Extremity Severity Score (MESS) and likelihood of requiring a tourniquet (p = 0.0013) but not between MESS and likelihood of receiving a tourniquet (p = 0.1055). There was also a significant association between wrongly placed tourniquets and the type of providers who placed them [first responders, p = 0.0029; Emergency Medicine Technicians (EMTs), p = 0.0001]. CONCLUSIONS: Tourniquets are being used inappropriately in the Hartford prehospital setting. Misuse is associated with both EMTs and first responders, highlighting the need for better training and more consistent protocols.

The Voltage Activation of Cortical KCNQ Channels Depends on Global PIP2 Levels.

The slow afterhyperpolarization (sAHP) is a calcium-activated potassium conductance with critical roles in multiple physiological processes. Pharmacological and genetic data suggest that KCNQ channels partly mediate the sAHP. However, these channels are not typically open within the observed voltage range of the sAHP. Recent work has shown that the sAHP is gated by increased PIP2 levels, which are generated downstream of calcium binding by neuronal calcium sensors such as hippocalcin. Here, we examined whether changes in PIP2 levels could shift the voltage-activation range of KCNQ channels. In HEK293T cells, expression of the PIP5 kinase PIPKIγ90, which increases global PIP2 levels, shifted the KCNQ voltage activation to within the operating range of the sAHP. Further, the sensitivity of this effect on KCNQ3 channels appeared to be higher than that on KCNQ2. Therefore, we predict that KCNQ3 plays an essential role in maintaining the sAHP under low PIP2 conditions. In support of this notion, we find that sAHP inhibition by muscarinic receptors that increase phosphoinositide turnover in neurons is enhanced in Kcnq3-knockout mice. Likewise, the presence of KCNQ3 is essential for maintaining the sAHP when hippocalcin is ablated, a condition that likely impairs PIP2 generation. Together, our results establish the relationship between PIP2 and the voltage dependence of cortical KCNQ channels (KCNQ2/3, KCNQ3/5, and KCNQ5), and suggest a possible mechanism for the involvement of KCNQ channels in the sAHP.

Potent KCNQ2/3-specific channel activator suppresses in vivo epileptic activity and prevents the development of tinnitus.

Voltage-gated Kv7 (KCNQ) channels are voltage-dependent potassium channels that are activated at resting membrane potentials and therefore provide a powerful brake on neuronal excitability. Genetic or experience-dependent reduction of KCNQ2/3 channel activity is linked with disorders that are characterized by neuronal hyperexcitability, such as epilepsy and tinnitus. Retigabine, a small molecule that activates KCNQ2-5 channels by shifting their voltage-dependent opening to more negative voltages, is an US Food and Drug Administration (FDA) approved anti-epileptic drug. However, recently identified side effects have limited its clinical use. As a result, the development of improved KCNQ2/3 channel activators is crucial for the treatment of hyperexcitability-related disorders. By incorporating a fluorine substituent in the 3-position of the tri-aminophenyl ring of retigabine, we synthesized a small-molecule activator (SF0034) with novel properties. Heterologous expression of KCNQ2/3 channels in HEK293T cells showed that SF0034 was five times more potent than retigabine at shifting the voltage dependence of KCNQ2/3 channels to more negative voltages. Moreover, unlike retigabine, SF0034 did not shift the voltage dependence of either KCNQ4 or KCNQ5 homomeric channels. Conditional deletion of Kcnq2 from cerebral cortical pyramidal neurons showed that SF0034 requires the expression of KCNQ2/3 channels for reducing the excitability of CA1 hippocampal neurons. Behavioral studies demonstrated that SF0034 was a more potent and less toxic anticonvulsant than retigabine in rodents. Furthermore, SF0034 prevented the development of tinnitus in mice. We propose that SF0034 provides, not only a powerful tool for investigating ion channel properties, but, most importantly, it provides a clinical candidate for treating epilepsy and preventing tinnitus.