Kratom-Induced Acute Respiratory Distress Syndrome (ARDS).

The alkaloid derivatives of Mitragyna speciosa, commonly known as kratom, pose a threat to society due to its potential for abuse, adverse reactions and tendency to be used as self-medication for opioid withdrawal, pain and mood disorders. A number of deaths have been reported along with complications such as respiratory depression, cardiopulmonary arrest, torsade de pointes and seizures. Its various effects and potential are yet to be fully studied. We describe the case of a healthy young male who presented with progressive respiratory failure requiring mechanical ventilation. Imaging revealed multifocal lung infiltrates while extensive infectious and cardiac work-up was negative. Based on the clinical course, a diagnosis of acute respiratory distress syndrome (ARDS) caused by kratom was made. The patient showed gradual clinical improvement and was weaned off supplemental oxygen. This case highlights yet another adverse reaction to kratom and the growing threat posed by its use. LEARNING POINTS: Kratom is a herbal supplement with opioid-like effects at high doses and stimulant effects at low doses.It is most commonly used to self-treat opioid withdrawal, mood disorders and pain.Acute respiratory distress syndrome (ARDS) is one of the adverse effects of kratom, which also include kratom withdrawal syndrome, seizures, rhabdomyolysis, torsades de pointes and sudden death.Kratom has growing abuse potential; the FDA is acting to prevent its use and recommends healthcare professionals voluntarily report any adverse reactions.

The Management of Acute Onset Complete Heart Block and Atrial Flutter in a Patient with COVID-19.

Coronavirus disease (COVID-19) has infected millions of people worldwide. Its cardiac presentations include myocarditis, arrhythmias and structural heart changes even in young and healthy individuals. The long-term sequelae of these manifestations are unknown. We describe a unique combination of complete heart block and atrial flutter in the setting of COVID-19. SARS-CoV-2 virulence mechanisms can cause fibrosis in the myocardium resulting in loss of sinus node dominance. The paradoxical finding of atrial flutter and complete heart block is very rare. Prompt cardiac evaluation and electrophysiological testing are important. Cardiac magnetic resonance imaging (cMRI) and endomyocardial biopsies are the gold standard investigations. Anticoagulation should be administered until atrioventricular synchrony is achieved. LEARNING POINTS: Simultaneous atrial flutter and third-degree atrioventricular block (AVB) caused by COVID-19 infection should be treated with a pacemaker according to heart block guidelines.During the COVID-19 pandemic, we recommend leadless pacemaker implantation for third-degree AVB as it has a lower risk of infection compared with traditional percutaneous procedures.Due to a lack of long-term data, patients with cardiac manifestations from COVID-19 require close follow-up with individualized surveillance schedules.

Refractory familial hypokalaemic periodic paralysis leading to cardiovascular compromise.

Familial hypokalaemic periodic paralysis (FHPP) is a rare neuromuscular disorder that is classified under periodic paralysis (PP), which is characterised by episodes of muscle weakness. Common triggers include intense exercise, fasting or consumption of carbohydrate-rich meals. Hypokalaemic PP has an incidence of 1 in 100 000; despite the temporal association, cardiac manifestations are exceedingly rare. We present a case of FHPP, a channelopathy presenting with severe refractory hypokalaemia. The challenges with our patient were maintaining potassium levels within normal ranges and initiating a close follow-up plan. Due to the lack of clinical guidance in our case, many aspects of care, including surveillance, medications and genetic testing, remain unaddressed. Medical management includes aggressive correction with supplements, potassium-sparing diuretics and carbonic anhydrase inhibitors. Severe cases of dysrhythmias, especially ventricular fibrillation, require electrophysiology evaluation and possible implantation of a defibrillator to prevent sudden cardiac death.

A 29-Year-Old Male with a Fatal Case of COVID-19 Acute Respiratory Distress Syndrome (CARDS) and Ventilator-Induced Lung Injury (VILI).

BACKGROUND COVID-19 patients that develop acute respiratory distress syndrome (ARDS) "CARDS" behave differently compared to patients with classic forms of ARDS. Recently 2 CARDS phenotypes have been described, Type L and Type H. Most patients stabilize at the milder form, Type L, while an unknown subset progress to Type H, resembling full-blown ARDS. If uncorrected, phenotypic conversion can induce a rapid downward spiral towards progressive lung injury, vasoplegia, and pulmonary shrinkage, risking ventilator-induced lung injury (VILI) known as the "VILI vortex". No cases of in-hospital phenotypic conversion have been reported, while ventilation strategies in these patients differ from the lung-protective approaches seen in classic ARDS. CASE REPORT A 29-year old male was admitted with COVID-19 pneumonia complicated by severe ARDS, multi-organ failure, cytokine release syndrome, and coagulopathy during his admission. He initially resembled CARDS Type L case, although refractory hypoxemia, fevers, and a high viral burden prompted conversion to Type H within 8 days. Despite ventilation strategies, neuromuscular blockade, inhalation therapy, and vitamin C, he remained asynchronous to the ventilator with volumes and pressures beyond accepted thresholds, eventually developing a fatal tension pneumothorax. CONCLUSIONS Patients that convert to Type H can quickly enter a spiral of hypoxemia, shunting, and dead-space ventilation towards full-blown ARDS. Understanding its nuances is vital to interrupting phenotypic conversion and entry into VILI vortex. Tension pneumothorax represents a poor outcome in patients with CARDS. Further research into monitoring lung dynamics, modifying ventilation strategies, and understanding response to various modes of ventilation in CARDS are required to mitigate these adverse outcomes.

Effect of oxygenation modalities among patients with postoperative respiratory failure: a pairwise and network meta-analysis of randomized controlled trials.

BACKGROUND: Postoperative respiratory failure is associated with increased perioperative complications. Our aim is to compare outcomes between non-invasive ventilation (NIV), high-flow nasal cannula (HFNC), and standard oxygen in patients at high-risk for or with established postoperative respiratory failure. METHODS: Electronic databases including PubMed, Embase, and the Cochrane Library were reviewed from inception to September 2019. We included only randomized controlled trials (RCTs) that compared NIV, HFNC, and standard oxygen in patients at high risk for or with established postoperative respiratory failure. We performed a Bayesian network meta-analysis to calculate the odds ratio (OR) and Bayesian 95% credible intervals (CrIs). RESULTS: Nine RCTs representing 1865 patients were included (the mean age was 61.6 ± 10.2 and 64.4% were males). In comparison with standard oxygen, NIV was associated with a significant reduction in intubation rate (OR 0.23; 95% Cr.I. 0.10-0.46), mortality (OR 0.45; 95% Cr.I. 0.27-0.71), and intensive care unit (ICU)-acquired infections (OR 0.43, 95% Cr.I. 0.25-0.70). Compared to standard oxygen, HFNC was associated with a significant reduction in intubation rate (OR 0.28, 95% Cr.I. 0.08-0.76) and ICU-acquired infections (OR 0.41; 95% Cr.I. 0.20-0.80), but not mortality (OR 0.58; 95% Cr.I. 0.26-1.22). There were no significant differences between HFNC and NIV regarding different outcomes. In a subgroup analysis, we observed a mortality benefit with NIV over standard oxygen in patients undergoing cardiothoracic surgeries but not in abdominal surgeries. Furthermore, in comparison with standard oxygen, NIV and HFNC were associated with lower intubation rates following cardiothoracic surgeries while only NIV reduced the intubation rates following abdominal surgeries. CONCLUSIONS: Among patients with post-operative respiratory failure, HFNC and NIV were associated with significantly reduced rates of intubation and ICU-acquired infections compared with standard oxygen. Moreover, NIV was associated with reduced mortality in comparison with standard oxygen.

Noninvasive Oxygenation Strategies in Immunocompromised Patients With Acute Hypoxemic Respiratory Failure: A Pairwise and Network Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Acute hypoxemic respiratory failure (AHRF) is a leading cause of intensive care unit (ICU) admission among immunocompromised patients. Invasive mechanical ventilation is associated with increased morbidity and mortality. OBJECTIVE: To evaluate the efficacy of various oxygenation strategies including noninvasive ventilation (NIV), high-flow nasal cannula (HFNC), and conventional oxygen therapy in immunocompromised patients with AHRF. METHODS: Electronic databases including PubMed, Embase, and the Cochrane Library were reviewed from inception to December 2018. We included all randomized controlled trials (RCTs) comparing different modalities of initial oxygenation strategies in immunocompromised patients with AHRF. Our primary outcome was the need for intubation and invasive mechanical ventilation while secondary outcomes were ICU acquired infections and short- and long-term mortality. Data were extracted separately and independently by 2 reviewers. We performed a Bayesian network meta-analysis to calculate odds ratio (OR) and Bayesian 95% credible intervals (CrIs). RESULTS: Nine RCTs were included (1570 patients, mean age 61.1 ± 13.8 years with 64% male). Noninvasive ventilation was associated with a significantly reduced intubation rate compared with standard oxygen therapy (OR: 0.53; 95% CrI: 0.26-0.91). There were no significant reductions of intubation between NIV versus HFNC (OR: 0.83; 95% CrI: 0.35-2.11) or HFNC versus standard oxygen therapy (OR: 0.65; 95% CrI: 0.26-1.24). There were no significant differences between all groups regarding short-term (28-day or ICU) mortality or long-term (90-day or hospital) mortality or ICU-acquired infections (P > 0.05). CONCLUSION: Among immunocompromised patients with AHRF, NIV was associated with a significant reduction of intubation compared with standard oxygen therapy. There were no significant differences among all oxygenation strategies regarding mortality and ICU-acquired infections.

Extended duration of thromboprophylaxis for medically ill patients: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: The benefit of extended-duration thromboprophylaxis in patients hospitalised for acute medical illness beyond hospital stay remains controversial. AIMS: To perform a meta-analysis of randomised controlled trials (RCT) in order to examine the efficacy and safety of extended-duration anticoagulation for venous-thromboembolism (VTE) prophylaxis in this high-risk population. METHODS: An electronic database search was conducted to include all RCT comparing between extended-duration versus short-duration prophylactic anticoagulation in medically ill patients. The primary efficacy outcome was the composite events of asymptomatic deep vein thrombosis (DVT), symptomatic VTE and death from VTE-related causes. RESULTS: Five RCT were included totalling 40 124 patients, with a mean age of 71 years and 51% were male. In comparison to standard-duration therapy, extended-duration thromboprophylaxis was associated with a significant reduction in the primary efficacy outcome (risk ratio (RR) 0.75; 95% confidence interval (CI) 0.67-0.85; P < 0.01), symptomatic VTE (RR 0.53; 95% CI 0.33-0.84; P < 0.01) and asymptomatic DVT (RR 0.81; 95% CI 0.71-0.94; P < 0.01). However, there were no significant differences between both groups with regard to VTE-related death (RR 0.81; 95% CI 0.60-1.10; P = 0.18) or all-cause death (RR 0.97; 95% CI 0.88-1.08; P = 0.64). In contrast, extended-duration thromboprophylaxis was associated with an increased risk of major bleeding (RR 2.04; 95% CI 1.42-2.91; P < 0.01) and non-major clinically relevant bleeding (RR 1.81; 95% CI 1.29-2.53; P < 0.01). CONCLUSIONS: Among hospitalised medically ill patients, prolonging venous thromboprophylaxis was associated with a decreased risk of composite events of the primary efficacy outcome and increased risk of bleeding with no significant difference in VTE-related death.

Initial Noninvasive Oxygenation Strategies in Subjects With De Novo Acute Hypoxemic Respiratory Failure.

BACKGROUND: De novo hypoxemic respiratory failure is defined as significant hypoxemia in the absence of chronic lung disease such as COPD, and excluding respiratory failure occurring in the immediate postoperative or postextubation period. We aimed to evaluate the efficacy of various oxygenation strategies including noninvasive ventilation (NIV), high-flow nasal cannula (HFNC), and conventional oxygen therapy in patients with de novo hypoxemic respiratory failure. METHODS: We performed electronic database searches of PubMed, Cochrane Library, and Embase from inception to December 2018 to include randomized controlled trials that compared various oxygenation strategies in cases of de novo hypoxemic respiratory failure occurring in adult subjects without a preexisting chronic lung disease and excluding respiratory failure in the immediate postoperative or postextubation periods. We performed a Bayesian network meta-analysis to calculate odds ratio (OR) and Bayesian 95% credible intervals (CrI). RESULTS: 16 studies were included, involving 2,180 subjects with a mean age of 61 ± 17 y (66% were male; 46% of the included subjects were treated with conventional oxygen, 27.8% were treated with NIV, and 25.8% were treated with HFNC). Compared to conventional oxygen, NIV was associated with reduced intubation rates (OR 0.42, 95% CrI 0.26-0.62) but no significant reduction in short-term (OR 0.73, 95% CrI 0.47-1.02) or long-term mortality (OR 0.60, 95% CrI 0.29-1.06). There was no significant difference between NIV and HFNC or between HFNC and conventional oxygen regarding all outcomes. In a sensitivity analysis, the results remained consistent after exclusion of studies that included subjects with respiratory failure secondary to cardiogenic pulmonary edema. CONCLUSION: Among subjects with hypoxemic respiratory failure, NIV was associated with a significant reduction in intubation rates but not short- or long-term mortality when compared to conventional oxygen therapy. There was no significant difference between NIV and HFNC or between HFNC and conventional oxygen regarding all outcomes.

Haloperidol for the management of delirium in adult intensive care unit patients: A systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Delirium commonly presents as a complication in critically ill patients. Our aim is to perform a meta-analysis investigating the role of haloperidol versus placebo in management (treatment and prophylaxis), of delirium in intensive care unit (ICU). MATERIALS AND METHODS: Our study is a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing haloperidol versus placebo for treatment and/or prophylaxis of ICU-related delirium. RESULTS: Six RCTs representing 2552 patients. There was no significant difference between haloperidol and placebo-treated patients in short-term all-cause mortality (risk ratio [RR] 0.96; 95% confidence interval [CI] 0.81-1.14; P = 0.67), incidence of delirium (RR 0.93; 95% CI 0.65-1.34; P = 0.70), ICU length of stay (Mean difference [MD] 0.00 days; 95% CI -0.82-0.83; P = 0.99), or delirium/coma-free days (MD 0.09; 95% CI -0.05-0.24; P = 0.21). Haloperidol was not associated with increased risk for serious adverse events (RR 0.65; 95% CI 0.23-1.88; P = 0.43), QTc prolongation (RR 0.87; 95% CI 0.63-1.19; P = 0.38), or extrapyramidal symptoms (RR 0.84; 95% CI 0.57-1.23; P = 0.37). CONCLUSION: Among critically ill patients, haloperidol administration compared with placebo does not significantly affect short-term mortality, incidence of delirium, ICU length of stay, or delirium or coma-free days. Additionally, there was no increased risk of adverse events.

Lung lobar collapse as the first manifestation of pulmonary epithelioid haemangioendothelioma diagnosed with fibreoptic bronchoscopy.

Pulmonary epithelioid haemangioendothelioma (PEH) is a rare tumour of endothelial origin that usually occurs in the lung and liver. It usually presents as bilateral multiple nodular lesions. We report a middle-aged woman with a unique presentation of PEH with lung lobar collapse. The diagnosis was made with fibreoptic bronchoscopy rather than video-assisted thoracoscopy. Clinicians and pathologists should be aware of rare conditions that can present as lung lobar collapse.

GM-CSF provides autocrine protection for murine alveolar epithelial cells from oxidant-induced mitochondrial injury.

Exposure of mice to hyperoxia induces alveolar epithelial cell (AEC) injury, acute lung injury and death. Overexpression of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the lung protects against these effects, although the mechanisms are not yet clear. Hyperoxia induces cellular injury via effects on mitochondrial integrity, associated with induction of proapoptotic members of the Bcl-2 family. We hypothesized that GM-CSF protects AEC through effects on mitochondrial integrity. MLE-12 cells (a murine type II cell line) and primary murine type II AEC were subjected to oxidative stress by exposure to 80% oxygen and by exposure to H(2)O(2). Exposure to H(2)O(2) induced cytochrome c release and decreased mitochondrial reductase activity in MLE-12 cells. Incubation with GM-CSF significantly attenuated these effects. Protection induced by GM-CSF was associated with Akt activation. GM-CSF treatment also resulted in increased expression of the antiapoptotic Bcl-2 family member, Mcl-1. Primary murine AEC were significantly more tolerant of oxidative stress than MLE-12 cells. In contrast to MLE-12 cells, primary AEC expressed significant GM-CSF at baseline and demonstrated constitutive activation of Akt and increased baseline expression of Mcl-1. Treatment with exogenous GM-CSF further increased Akt activation and Mcl-1 expression in primary AEC. Conversely, suppression of AEC GM-CSF expression by use of GM-CSF-specific small interfering RNA resulted in decreased tolerance of oxidative stress, Furthermore, silencing of Mcl-1 prevented GM-CSF-induced protection. We conclude that GM-CSF protects alveolar epithelial cells against oxidative stress-induced mitochondrial injury via the Akt pathway and its downstream components, including Mcl-1. Epithelial cell-derived GM-CSF may contribute to intrinsic defense mechanisms limiting lung injury.