Jon-Emile S. Kenny MD [@heart_lung] “What time is this, to trade the handshake for the fist?” -Joni Mitchell Background As remarked by the authors of the recent PLUS trial, a systematic review and meta-analysis of randomized controlled trials comparing balanced resuscitation fluid to 0.9% saline was reported in the New England Journal of Medicine Evidence. This [… read more]
Jon-Emile S. Kenny MD [@heart_lung] “The world wavered and quivered and threatened to burst into flames.” -Virginia Woolf Background Intravenous fluid therapy is one of the most commonly-performed interventions in all of critical care medicine. Numerous trials over the last 20 years have attempted to identify the ideal fluid for those in the intensive care unit, [… read more]
Jon-Emile S. Kenny MD [@heart_lung] “… but prejudices, like odorous bodies, have a double existence, both solid and subtle – solid as the pyramids, subtle as the twentieth echo of an echo, or as the memory of hyacinths which once scented the darkness.” -Mary Ann Evans Background As previously described, the SARS-CoV-2 main protease inhibitor [Mpro] [… read more]
Jon-Emile S. Kenny MD [@heart_lung] “When she smiles without her teeth in place she looks like a witch. But with them in her mouth she’s very pretty.” -Judy Blume Basic Biology The SARS-CoV-2 genome encodes structural proteins [i.e., spike, envelope, membrane, nucleocapsid] and polyproteins [i.e., pp1a and pp1ab]. When the guts of SARS-CoV-2 spew into a [… read more]
Jon-Emile S. Kenny MD [@heart_lung] “If you’re afraid of butter, use cream.” -Julia Child Background Early observational studies and the RECOVERY collaborative group initially demonstrated the benefit of corticosteroid therapy in oxygen-requiring, COVID-19-patients; additional randomized studies as well as a meta-analysis of these reports corroborated this. Yet the dosing of corticosteroids across the above studies was [… read more]
Jon-Emile S. Kenny MD [@heart_lung] “… Sartre tells us that man makes himself this lack of being in order that there might be being.” -Simone de Beauvoir Background Like many early, proposed therapies for COVID-19, inhaled corticosteroids [ICS] had suggestive, conflicting evidence. For example, in a very large observational investigation – the OpenSAFELY platform – patients with both [… read more]
Jon-Emile S. Kenny MD [@heart_lung] “In those years, truth was elusive – as was my own faith that I could recognize and contain it.” -Mary Oliver Previously, the very basic underpinnings of fluvoxamine as a pharmacological method to quell cytokine unruliness was outlined. In brief, fluvoxamine is a sigma-1-receptor [S1R] agonist – an effect that opposes [… read more]
Jon-Emile S. Kenny MD [@heart_lung] “He walked away across the room, his cowboy boots echoing like pistol shots.” -Sylvia Plath Background Implicit in resuscitation is speed. Throughout training we are zealously instructed that ‘time is tissue’ for all manners of compromised perfusion. We envision spendthrift mitochondria chewing through oxygen without regard to withering supply; as such, [… read more]
Jon-Emile S. Kenny MD [@heart_lung] “May I be the tiniest nail in the house of the universe, tiny but useful.” -Mary Oliver Background The use of ‘balanced’ intravenous fluids as compared to 0.9% saline – so-called ‘normal’ saline – has garnered much scientific interest in the last half-decade. Propelling some of this curiosity is a newfound [… read more]
Jon-Emile S. Kenny MD [@heart_lung] “Apocalypse is played out now on a personal scale; it is not in the sky above us, but in our bed.” -Mark Doty Introduction With a proposed pathway coupling pathogen-associated molecular patterns to the elaboration of pro-inflammatory cytokines, sketched lightly in part 1, this segment ties murine biomolecular theory to human [… read more]
Jon-Emile S. Kenny MD [@heart_lung] “You see, we have a kind of allergy to the past; it’s our national disease, and the very assurance with which you insist that the past is within the present is likely to seem quite repellent, even offensive, to these new readers.” -Richard Howard Introduction Early in the COVID-19 pandemic, the [… read more]
Jon-Emile S. Kenny MD [@heart_lung] “Booksellers are the most valuable destination for the lonely, given the numbers of books that were written because authors couldn’t find anyone to talk to.” – Alain de Botton Introduction An important reason for treating both tuberculosis and HIV with multiple pharmacological agents is the ability of these infectious scourges to [… read more]
Jon-Emile S. Kenny MD [@heart_lung] “Let us try to assume our fundamental ambiguity.” -Simone de Beauvoir When the pre-peer review RECOVERY trial was released in mid-June of this year, clinicians lost equipoise to enroll hospitalized patients receiving at least oxygen for COVID-19 into trials including a treatment arm without corticosteroids. This brought to an early-halt three [… read more]
A combination of vitamins C and B1 with corticosteroids didn’t prevent organ failure in septic shock, the ACTS trial showed. The intervention improved the Sequential Organ Failure Assessment (SOFA) score 4.7 points compared with a 4.1-point improvement with placebo over the 72 hours after enrollment, which was not significant at P=0.12 for interaction, reported Michael Donnino, [… read more]
Jon-Emile S. Kenny MD [@heart_lung] “This whole thing is not about heroism. It’s about decency. It may seem a ridiculous idea, but the only way to fight the plague is with decency.” -Albert Camus Background In 2013, Dünser and colleagues communicated a rogue viewpoint in shock resuscitation – let us do away with strict macro-hemodynamic goals [… read more]
A new randomized trial showed no benefit from intravenous vitamin C in patients with sepsis, but delays in treatment baked into the trial design will keep hope alive for true believers in the novel therapy. Vitamin C, hydrocortisone, and thiamine have been promoted as a lifesaving adjunctive therapy for septic shock, based on anecdotal data [… read more]
Vitamin D supplementation brought no measurable benefits to vitamin D-deficient critically ill patients, in a large randomized trial published in the New England Journal of Medicine. Vitamin D supplementation has long been hoped for as a potential lifesaving therapy in critical illness. Many critically ill patients are vitamin D deficient, and deficiency increases the risk [… read more]
Jon-Emile S. Kenny MD [@heart_lung] “Dying is a wild night and a new road.” -Emily Dickinson Background In 2006, a recruitment maneuver to achieve an ‘open lung’ was circulated; it has since been dubbed ‘stairway recruitment’ given its stepwise upthrusts in airway pressure [see figure 1]: Plodding up this ladder of airway pressure was meant to [… read more]
Inhaled corticosteroids have been the mainstay of treatment for persistent asthma for decades. A new trial suggests that for the ~50% of asthma patients with low sputum eosinophils, inhaled steroids are no better than placebo, and neither was tiotropium. Treatment with the inhaled glucocorticoid mometasone or the long-acting muscarinic antagonist tiotropium resulted in similar outcomes [… read more]
Beta-blockers have generally been considered safe and beneficial for patients with COPD, but a new randomized trial calls that assumption into doubt. The use of oral beta blockers without a cardiac indication appeared to double the risk of hospitalization for people experiencing a COPD exacerbation. Authors randomized 532 patients with moderate or severe COPD with [… read more]
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