Randomized Controlled Trials

Mar 072022
 
Balanced Crystalloids Probably Reduce Mortality in the Critically-Ill

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]

Feb 282022
 
Balanced Fluid Resuscitation for the Critically-Ill: the PLUS study mirrors the BaSICS

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]

Jan 302022
 
Nirmatrelvir-Ritonavir for ‘Standard Risk’ COVID-19

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]

Jan 292022
 
EPIC-HR Evaluates Nirmatrelvir-Ritonavir for COVID-19

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]

Jan 022022
 
COVID STEROID 2 Trial Investigates Dexamethasone 6 mg or 12 mg in COVID-19

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]

Nov 182021
 
PRINCIPLE Investigators Study Inhaled Budesonide for COVID-19

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]

Oct 312021
 
The TOGETHER Trial Evaluates Fluvoxamine for COVID-19

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]

Sep 092021
 
Back to the BaSICS: does the infusion rate of a fluid bolus affect mortality?

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]

Sep 012021
 
Another 0.9% Saline versus Balanced Solution Trial: BaSICS released

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]

Mar 312021
 
On Cytokines, Fluvoxamine and COVID-19 – Part 2

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]

Mar 282021
 
On Cytokines, Fluvoxamine and COVID-19 – Part 1

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]

Jan 292021
 
A Cursory Review of Casirivimab and Imdevimab for COVID-19

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]

Sep 102020
 
More on Corticosteroids in COVID-19 – Part 1: REMAP-CAP, CAPE-COVID & CoDEX trials

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]

Sep 062020
 
Vitamin C, steroids, thiamine for septic shock: no benefit in ACTS trial

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]

May 242020
 
Does the 65 Trial Dial Down the Mean Arterial Pressure in Sepsis?

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]

Feb 092020
 
Vitamin C didn't improve septic shock in VITAMINS trial

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]

Jan 202020
 
Adding Vitamin D no help in critical illness, even in deficient patients

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]

Dec 272019
 
The PHARLAP Trial: Recruitment Maneuvers Buy Stairway to Heaven?

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]

Dec 122019
 
Inhaled steroids may not work for half of asthma patients

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]

Nov 172019
 
Beta-blockers doubled risk of hospitalization from COPD exacerbations (BLOCK-COPD)

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]