A systematic review of interventions for resuscitation following drowning.

Objectives: The International Liaison Committee on Resuscitation, in collaboration with drowning researchers from around the world, aimed to review the evidence addressing seven key resuscitation interventions: 1) immediate versus delayed resuscitation; (2) compression first versus ventilation first strategy; (3) compression-only CPR versus standard CPR (compressions and ventilations); (4) ventilation with and without equipment; (5) oxygen administration prior to hospital arrival; (6) automated external defibrillation first versus cardiopulmonary resuscitation first strategy; (7) public access defibrillation programmes. Methods: The review included studies relating to adults and children who had sustained a cardiac arrest following drowning with control groups and reported patient outcomes. Searches were run from database inception through to April 2023. The following databases were searched Ovid MEDLINE, Pre-Medline, Embase, Cochrane Central Register of Controlled Trials. Risk of bias was assessed using the ROBINS-I tool and the certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. The findings are reported as a narrative synthesis. Results: Three studies were included for two of the seven interventions (2,451 patients). No randomised controlled trials were identified. A retrospective observational study reported in-water resuscitation with rescue breaths improved patient outcomes compared to delayed resuscitation on land (n = 46 patients, very low certainty of evidence). The two observational studies (n = 2,405 patients), comparing compression-only with standard resuscitation, reported no difference for most outcomes. A statistically higher rate of survival to hospital discharge was reported for the standard resuscitation group in one of these studies (29.7% versus 18.1%, adjusted odds ratio 1.54 (95% confidence interval 1.01-2.36) (very low certainty of evidence). Conclusion: The key finding of this systematic review is the paucity of evidence, with control groups, to inform treatment guidelines for resuscitation in drowning.

Effects of personal protective equipment on cardiopulmonary resuscitation quality and outcomes: A systematic review.

Background: The impact of wearing personal protective equipment (PPE) during cardiopulmonary resuscitation (CPR) on CPR quality and patient outcomes is unclear. This systematic review aimed to examine whether wearing PPE during resuscitation affects patient outcomes, CPR quality and rescuer fatigue. Methods: In this review registered in PROSPERO (CRD42022347746), we searched Medline, EMBASE and Cochrane library between 2000 and 2022. The inclusion criteria were studies: in actual or simulated cardiac arrest; comparing PPE with no PPE; and randomised controlled trials and observational studies with a English abstract. Risk of bias was assessed using Cochrane's Risk of Bias-2 and ROBINS-I tools and outcomes assessed with GRADE. We conducted a meta-analysis according to the study design. Quantitative data synthesis was done using a random-effect model incorporating the potential heterogeneity. Results: A total of 17 simulation-based studies and 1 clinical study were included. All outcomes were judged to be very low certainty of evidence, subject to high risk of bias. The clinical study showed no difference in survival comparing enhanced and conventional PPE. Meta-analysis of 11 RCTs and 6 observational studies found no difference in CPR quality in rescuers wearing PPE compared with no PPE. Pooled rescuer fatigue was significantly worse in the PPE group (mean difference, 2.7 VAS score out of 10; 95% CI, 1.4-4.0). Conclusions: PPE was not associated with reduced CPR quality or lower cardiac arrest survival. Rescuers wearing PPE may report more fatigue. This finding was mainly derived from simulation studies, additional clinical studies are needed.

Ultra-high dose intravenous nitroglycerin in an ESRD patient with acutely decompensated heart failure.

Acute cardiogenic pulmonary edema is a highly unstable and potentially lethal condition that is most commonly associated with markedly elevated blood pressure (BP). Use of nitrates, diuretics, and non-invasive positive pressure ventilatory support are the mainstays of early intervention and stabilization. Use of high-dose bolus intravenous nitroglycerin, which causes both preload and afterload reduction, has shown significant promise in studies to date, reducing the need for endotracheal intubation (ETI) and intensive care unit admission. To date, the highest recorded total dose of nitroglycerin used during the initial stabilization of acute pulmonary edema has been 20 mg. Here, we describe a patient with end-stage renal disease who developed acute cardiogenic pulmonary edema and received a total of 59 mg nitroglycerin (56 mg push dose intravenous + 3 mg intravenous drip) over 41 minutes leading to successful stabilization and avoidance of ETI, facilitating rapid initiation of emergent hemodialysis.

Decompression sickness responsive to delayed treatment with hyperbaric oxygen: a case report of two divers.

With the increasing popularity of recreational scuba diving, rare complications are becoming more commonly encountered. Although diving is generally safe, novice divers may be unfamiliar with the potential hazards of scuba diving and the resulting sequelae. Dive-related injuries are commonly due to barotrauma or from breathing gas at increased pressures, resulting in decompression illness (DCI), a term that includes both decompression sickness (DCS) and arterial gas embolism (AGE). Symptoms can range from minor aches and pains to neurologic or cardiopulmonary complications resulting in death. Clinical symptoms and diagnosis may initially go unrecognized and can present in a delayed manner, often remote to the diving location. When DCI is suspected standard treatment with hyperbaric oxygen (HBO2) therapy should be considered immediately. Current literature questions the efficacy of delayed HBO2 therapy longer than 24-48 hours after symptom onset. Here we present a case of two divers who simultaneously experienced DCS and were both successfully treated after receiving delayed HBO2 therapy nearly eight days after initiation of symptoms.

Breaking open the case of one patient's acute left flank pain: nutcracker syndrome.

Acute flank and abdominal pain represent a common presenting complaint in the emergency department. The etiology can be broad, ranging from the chest to the groin, from benign to catastrophic. There are common causes such as nephrolithiasis and pyelonephritis for which more than 1 million Americans are diagnosed with in the United States each year.1 Other etiologies are more rare and difficult to diagnose. The following case discusses a rare syndrome involving a young man with flank pain and a few other symptoms.

Real World Evidence for Treatment of Hyperkalemia in the Emergency Department (REVEAL-ED): A Multicenter, Prospective, Observational Study.

BACKGROUND: Contemporary emergency department (ED) standard-of-care treatment of hyperkalemia is poorly described. OBJECTIVE: Our aim was to determine the treatment patterns of hyperkalemia management in the ED. METHODS: This multicenter, prospective, observational study evaluated patients aged ≥ 18 years with hyperkalemia (potassium [K+] level ≥ 5.5 mmol/L) in the ED from October 25, 2015 to March 30, 2016. K+-lowering therapies and K+ were documented at 0.5, 1, 2, and 4 h after initial ED treatment. The primary end point was change in K+ over 4 h. RESULTS: Overall, 203 patients were enrolled at 14 U.S.-based sites. The initial median K+ was 6.3 (interquartile range [IQR] 5.7-6.8) mmol/L and median time to treatment was 2.7 (IQR 1.9-3.5) h post-ED arrival. Insulin/glucose (n = 130; 64%) was frequently used to treat hyperkalemia; overall, 43 different treatment combinations were employed within the first 4 h. Within 4 h, the median K+ for patients treated with medications alone decreased from 6.3 (IQR, 5.8-6.8) mmol/L to 5.3 (4.8-5.7) mmol/L, while that for patients treated with dialysis decreased from 6.2 (IQR 6.0-6.6) mmol/L to 3.8 (IQR 3.6-4.2) mmol/L. Hypoglycemia occurred in 6% of patients overall and in 17% of patients with K+ > 7.0 mmol/L. Hyperkalemia-related electrocardiogram changes were observed in 23% of all patients; 45% of patients with K+ > 7.0 mmol/L had peaked T waves or widened QRS. Overall, 79% were hospitalized; 3 patients died. CONCLUSIONS: Hyperkalemia practice patterns vary considerably and, although treatment effectively lowered K+, only dialysis normalized median K+ within 4 h.

Combination therapy with insulin-like growth factor-1 and hypothermia synergistically improves outcome after transient global brain ischemia in the rat.

OBJECTIVES: Hypothermia has a well-established neuroprotective effect and offers a foundation for combination therapy for brain ischemia. The authors evaluated the effect of combination therapy with insulin-like growth factor-1 (IGF-1) and hypothermia on brain structure and function in the setting of global brain ischemia and reperfusion in rats. METHODS: Male Sprague-Dawley rats were randomly assigned to groups by a registrar. Animals were subjected to 8 minutes of global brain ischemia using bilateral carotid occlusion and systemic hypotension, followed by 7 days (Stage I dose studies) or 28 days (Stage II outcome studies) of reperfusion. Sham controls were subjected to surgery, but not ischemia. Stage II animals were randomized to no treatment, IGF-1 at the dose determined in Stage I, hypothermia (32°C for 4 hours), or a combination of IGF-1 and hypothermia. Stage II animals underwent 21 days of spatial memory testing. At 7 days (Stage I) or 28 days (Stage II), brains were harvested for counting of CA1 neurons. The primary Stage II outcome was a neurologic outcome index computed as the ratio of viable CA1 neurons per 300-µm field to the number of days to reach success criteria on the memory task. RESULTS: Stage I experiments confirmed the neuroprotective effect of the hypothermia protocol and IGF-1 at a dose of 0.6 U/kg. Stage II studies suggested that early neuroprotection with hypothermia and IGF-1 was not well maintained to 28 days and that combination therapy was more beneficial than either IGF-1 or hypothermia alone. Median and interquartile ranges (IQRs) of viable neurons per 300-µm field were 114 (IQR = 99.5 to 136) for sham, three (IQR = 2 to 4.8) for untreated ischemia, four (IQR = 3 to 70.25) for ischemia treated with IGF-1 alone, 25 (IQR = 3 to 70) for ischemia treated with hypothermia alone, and 78 (IQR 47.3 to 97.5) for ischemia treated with combination therapy. Days to memory success criteria were 13.6 (IQR = 11.5 to 15.5 days) for sham, 23.5 (IQR = 20 to 25.5 days) for untreated ischemia, 17.5 (IQR = 15.5 to 25.5 days) for ischemia treated with IGF-1, 15 (IQR = 14.5 to 21 days) for ischemia treated with hypothermia, and 13.5 (IQR = 12.25 to 18.5 days) for ischemia treated with combination therapy. Neurologic outcome indices were 8.5 (IQR = 7.4 to 9.5) for sham, 0.14 (IQR = 0.08 to 0.2) for untreated ischemia, 0.18 (IQR = 0.17 to 4.6) for ischemia treated with IGF-1, 0.7 (IQR = 0.2 to 4.8) for ischemia treated with hypothermia, and 5.7 (IQR = 3.3 to 6.2) for ischemia treated with combination therapy. Statistically significant differences in neuron counts, days to memory test criteria, and outcome index were found between sham and untreated ischemic animals. Of the three treatment regimens, only combination therapy showed a statistically significant difference from the untreated ischemic group for neuronal salvage (p = 0.02), days to criteria (p = 0.043), and outcome index (p = 0.014). CONCLUSIONS: Combination therapy with IGF-1 (0.6 U/kg) and therapeutic hypothermia (32°C for 4 hours) at the onset of reperfusion synergistically preserves CA1 structure and function at 28 days after 8 minutes of global brain ischemia in healthy male rats.

The "Refrige-a-RAT-or": an accurate, inexpensive, and clinically relevant small animal model of therapeutic hypothermia.

BACKGROUND: Physical and molecular mechanisms for the neuroprotective effect of therapeutic hypothermia are not completely understood, and new therapeutic applications incorporating hypothermia remain to be developed and tested. Clinically relevant animal models of therapeutic hypothermia are not well established or consistent. OBJECTIVES: The objective was to develop and test an inexpensive small animal therapeutic hypothermia system that models those in widespread clinical use and verify that such a system confers neuroprotection in a rat model of global brain ischemia. METHODS: A water-cooled extracorporeal system and attendant anesthesia/sedation protocol were developed and tested. In Stage 1, animals were instrumented for brain, temporalis, and rectal temperature monitoring, and the system was tested for its effect on temperature and hemodynamics. In Stage 2, animals were instrumented for rectal temperature only, subjected to global brain ischemia by two-vessel occlusion and hypotension for 8 minutes, and given either sham therapy (37°C) or hypothermia (32°C) for 4 hours. Viable CA1 neurons were counted at 7 days. RESULTS: The system was well tolerated, provided exquisite control of animal core and brain temperatures, and conferred robust neuroprotection at 7 days. The median and interquartile ranges (IQRs) of viable neurons per 300-µm field were 130 (IQR = 128 to 135) for sham control, 19 (IQR = 15 to 30) for untreated ischemic animals, and 101 (IQR = 94 to 113) for ischemic animals treated with hypothermia (p < 0.05 for comparison between all groups). CONCLUSIONS: Like human protocols, this model incorporates sedation and analgesia, results in robust neuroprotection, is well tolerated, and offers exquisite temperature control. The system is noninvasive and inexpensive and offers a model that is similar to methods used in clinical practice. This system will be of interest to investigators using small animal models to examine neuroprotective mechanisms of hypothermia and translational strategies that combine hypothermia with targeted pharmacotherapy.

Physiological and biochemical defects in functional interactions of mitochondrial DNA polymerase and DNA-binding mutants of single-stranded DNA-binding protein.

Functional interactions between mitochondrial DNA polymerase (pol gamma) and mitochondrial single-stranded DNA-binding protein (mtSSB) from Drosophila embryos greatly enhance the overall activity of pol gamma by increasing primer recognition and binding and stimulating the rate of initiation of DNA strands (Farr, C. L., Wang, Y., and Kaguni, L. S. (1999) J. Biol. Chem. 274, 14779-14785). We show here that DNA-binding mutants of mtSSB are defective in stimulation of DNA synthesis by pol gamma. RNAi knock-down of mtSSB reduces expression to <5% of its normal level in Schneider cells, resulting in growth defects and in the depletion of mitochondrial DNA (mtDNA). Overexpression of mtSSB restores cell growth rate and the copy number of mtDNA, whereas overexpression of a DNA-binding and functionally impaired form of mtSSB neither rescues the cell growth defect nor the mtDNA depletion phenotype. Further development of Drosophila animal models, in which induced mtDNA depletion is manipulated by controlling exogenous expression of wild-type or mutant forms, will offer new insight into the mechanism and progression of human mtDNA depletion syndromes and possible intervention schemes.