Randomized Controlled Trials

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]

Nov 082019
 
Can C-reactive protein improve treatment for COPD exacerbations?

Use of C-reactive protein (CRP) in decision-making may reduce antibiotic use in COPD exacerbations, but not as a replacement for clinical judgment, a study suggested. Chronic obstructive pulmonary disease (COPD) exacerbations are characterized by increased inflammation in the airways and the body generally. C-reactive protein (CRP) is a serum test for inflammation, and has been [… read more]

Oct 312019
 
Vitamin C reduces mortality from sepsis with ARDS in CITRIS-ALI randomized trial ... ?

Vitamin C infusion has generated tremendous interest as an adjunctive treatment for patients with sepsis, since a widely publicized cohort study claimed vitamin C dramatically reduced sepsis-related mortality at a single institution. The publicity, the plausible pathophysiologic mechanism, and the lack of any therapy for sepsis have led many intensivists to prescribe the so-called Marik [… read more]

Oct 182019
 
Prolonged hypothermia improved neurologic outcomes after non-shockable cardiac arrests (HYPERION, CRICS-TRIGGERSEP)

Targeted temperature management (TTM, or therapeutic hypothermia) has become standard therapy after cardiac arrest, especially for ventricular tachycardia and fibrillation–so called shockable rhythms. A new randomized trial has shown that deep, prolonged cooling after cardiac arrest from non-shockable rhythms (PEA and asystole) improved neurologic outcomes. But how robust were the results, and should they change [… read more]

Sep 062019
 
Prophylactic IVC filters prevent PE in high-risk trauma patients, but were often unnecessary

Inferior vena cava filters placed prophylactically in patients hospitalized for trauma prevented symptomatic pulmonary embolism in those patients with persistent contraindications to anticoagulation, in a significant randomized trial. However, prophylactic IVC filter placement for all post-trauma patients did not improve outcomes generally. Trauma teams have always faced a difficult dilemma in the prevention and treatment [… read more]

May 302019
 
Neuromuscular blockade for ARDS was no help, in supine patients

Continuous neuromuscular blockade for severe ARDS became common practice after the ACURASYS trial (2010) showed it reduced mortality by an absolute 9%. A larger trial, ROSE, now finds no benefit of the therapy over usual care — but leaves lingering questions due to major design differences. The ROSE trial was a multicenter randomized trial in [… read more]