Category: Critical Care
Keywords: trauma, pneumothorax, positive pressure ventilation, invasive mechanical ventilation, tension pneumothorax (PubMed Search)
Posted: 1/14/2022 by Kami Windsor, MD
Click here to contact Kami Windsor, MD
Background: Conventional medical wisdom long held that patients with pneumothorax (PTX) who require positive pressure ventilation (PPV) should undergo tube thoracostomy to prevent enlarging or tension pneumothorax, even if otherwise they would be managed expectantly.1
Bottom Line: The cardiopulmonar-ily stable patient with small PTX doesn’t need empiric tube thoracostomy simply because they’re receiving positive pressure ventilation. If you are unlucky enough to still have them in your ED at day 5 in these COVID times, provide closer monitoring as the observation failure rate may increase dramatically around this time.
Category: Critical Care
Keywords: Calcium, Cardiac Arrest, ACLS, Code Blue (PubMed Search)
Posted: 1/5/2022 by Mark Sutherland, MD
Click here to contact Mark Sutherland, MD
There are several well known medications that we tend to give by default during cardiac arrests. It seems like for each of them, every few years someone does an RCT to see if they really help anybody, and we're all disappointed by what they find. Well... prepare to be disappointed again, I'm afraid.
These Danish authors randomized 391 patients in cardiac arrest to either calcium or saline (given IV or IO). They gave 2 doses of either calcium chloride or saline, with the first dose being along with the first epi dose. Primary outcome was ROSC. They also looked at modified Rankin at 30 and 90 days.
The trial was stopped early for harm. Now, we all know the dangers of interpreting studies that were stopped early, but this doesn't look great for calcium. 19% of the calcium group had ROSC compared to 27% of the saline group (p = 0.09). Percentage of patients alive, and with favorable mRS at 30 days also both favored the saline group (although also not statistically significantly). By the way, of the patients who had calcium levels sent, 74% in the calcium group, vs 2% in the saline group, were hypercalcemic. Whether that had anything to do with the outcome, we may never know.
Bottom Line: Is this saying that calcium hurts patients in cardiac arrest? Maybe... but I don't think this is high quality enough data to draw that conclusion. At the very least, however, just giving everyone in arrest calcium is probably not terribly helpful. If you have a reason to give it (known severe hypocalcemia, recent parathyroid surgery, suspected hyperkalemia, etc) then go for it, otherwise you can probably focus your resus on more important things.
Vallentin MF, Granfeldt A, Meilandt C, et al. Effect of Intravenous or Intraosseous Calcium vs Saline on Return of Spontaneous Circulation in Adults With Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial. JAMA. 2021;326(22):2268–2276. doi:10.1001/jama.2021.20929
Category: Critical Care
Posted: 12/28/2021 by Mike Winters, MBA, MD
Click here to contact Mike Winters, MBA, MD
The BOUGIE Trial
Driver BE, et al. Effect of use of a bougie vs endotracheal tube with stylet on successful intubation on the first attempt among critically ill patients undergoing tracheal intubation. JAMA. 2021. Published online December 8, 2021
Category: Critical Care
Keywords: bacterial infection, sepsis, Emergency Department, broad spectrum antibiotics (PubMed Search)
Posted: 12/14/2021 by Quincy Tran, MD, PhD
(Updated: 7/27/2024)
Click here to contact Quincy Tran, MD, PhD
When we initiate the sepsis bundle in the ED for patients with suspected sepsis, what probability that those patients who received broad spectrum antibiotics in the ED would have bacterial infection.
This study (Shappell et al) provides us with a glimpse of those number.
Settings: Retrospective study of adults presenting to 4 EDs in Massachusetts.
Patients: patients with suspected serious bacterial infection in ED, defined as blood cultures and initiation of at least one broad spectrum antibiotics. Random selection of 75 patients per hospital.
Patients were categorized in 4 groups:
Outcome: Prevalence of each category.
Study Results: 300 patients who received broad spectrum antibiotics.
3. For patients who were admitted to the ICU (P = 0.26)
a. Definite 16.5%
b. Likely 8.6%
c. Unlikely 16.4%
d. Definitely no 20.4%
4. Source of infection
Discussion:
Conclusion:
Approximately 30% of patients who had blood cultures drawn and received broad spectrum antibiotics in ED have low likelihood of bacterial infection.
Reference:
1. Shappell CN, Klompas M, Ochoa A, Rhee C; CDC Prevention Epicenters Program. Likelihood of Bacterial Infection in Patients Treated With Broad-Spectrum IV Antibiotics in the Emergency Department. Crit Care Med. 2021 Nov 1;49(11):e1144-e1150. doi: 10.1097/CCM.0000000000005090. PMID: 33967206; PMCID: PMC8516665.
2. Klein Klouwenberg PM, Cremer OL, van Vught LA, Ong DS, Frencken JF, Schultz MJ, Bonten MJ, van der Poll T. Likelihood of infection in patients with presumed sepsis at the time of intensive care unit admission: a cohort study. Crit Care. 2015 Sep 7;19(1):319. doi: 10.1186/s13054-015-1035-1. PMID: 26346055; PMCID: PMC4562354.
Category: Critical Care
Posted: 12/7/2021 by Caleb Chan, MD
Click here to contact Caleb Chan, MD
Clinical Pearls for Variceal Hemorrhage
-lower mortality with “restrictive” (Hgb 7-9 g/dL) rather than liberal strategy
-antibiotic “prophylaxis” reduces mortality
-no need to correct INR with FFP
-vasoactives (i.e. octreotide, somatostatin, terlipressin) alone may actually control bleeding
-for your ICU boarders...if persistent or severe rebleeding (despite endoscopic therapy), rescue TIPS is therapy of choice (call IR)
Zanetto A, Shalaby S, Feltracco P, et al. Recent advances in the management of acute variceal hemorrhage. Journal of Clinical Medicine. 2021;10(17):3818.
Category: Critical Care
Posted: 11/23/2021 by Duyen Tran, MD
(Updated: 7/27/2024)
Click here to contact Duyen Tran, MD
Myocarditis is a potentially fatal inflammatory disorder of the heart. Viral infection is the most common cause but can also result from toxic, autoimmune, or other infectious etiologies. Complications include life-threatening dysrhythmias, heart failure, and fulminant myocarditis. Typically affects young patients (20-50 years old).
ED management pearls
Gottlieb, Michael et al. "Diagnosis And Management Of Myocarditis: An Evidence-Based Review For The Emergency Medicine Clinician". The Journal Of Emergency Medicine, vol 61, no. 3, 2021, pp. 222-233.
Category: Critical Care
Keywords: OHCA, IHCA, targeted temperature management, therapeutic hypothermia, postcardiac arrest (PubMed Search)
Posted: 11/16/2021 by Kami Windsor, MD
Click here to contact Kami Windsor, MD
Fever has long been understood to be associated with worse outcomes in patients post-cardiac arrest. Whether ascribing to the goal of 33-34°C, 36°C, or simply <38°C, close monitoring and management of core temperatures are a tenet of post-cardiac arrest care.
A recently published study compared the effectiveness of several methods in maintaining temperatures <38°C…
Results:
Maintenance of temp <38°C:
Mean change in temp from baseline:
Limitations:
Bottom Line:
Category: Critical Care
Keywords: Hypothermia, Cardiac Arrest, TTM (PubMed Search)
Posted: 11/9/2021 by Mark Sutherland, MD
Click here to contact Mark Sutherland, MD
The debate around post-arrest management recently has revolved around whether therapeutic hypothermia should go cold, or LESS cold. But what if we went MORE cold? While recent TTM trials have compared temps such as 33 to 36 and 33 to 37.5 or less, a recent trial called CAPITAL CHILL looked at 34C vs 31C. There is a solid physiologic basis for cooling post-arrest patients, so do they do better if we lower their temp even further? Maybe we're not going cold enough with 33?
Bottom Line: No, 31C is not better than 34C for post-arrest patients. This study compared death and poor neurologic outcome at 180 days with 31 and 34C targets for post-arrest patients, and found no difference (in fact the 31C group did slightly, but not significantly, worse on the primary outcome, and worse on a few secondary outcomes).
While debate remains for 33 vs 36 vs afebrile, the literature does not currently support consideration of temps below 33.
Le May M, Osborne C, Russo J, So D, Chong AY, Dick A, Froeschl M, Glover C, Hibbert B, Marquis JF, De Roock S, Labinaz M, Bernick J, Marshall S, Maze R, Wells G. Effect of Moderate vs Mild Therapeutic Hypothermia on Mortality and Neurologic Outcomes in Comatose Survivors of Out-of-Hospital Cardiac Arrest: The CAPITAL CHILL Randomized Clinical Trial. JAMA. 2021 Oct 19;326(15):1494-1503. doi: 10.1001/jama.2021.15703. PMID: 34665203; PMCID: PMC8527358.
Category: Critical Care
Posted: 11/2/2021 by Mike Winters, MBA, MD
(Updated: 7/27/2024)
Click here to contact Mike Winters, MBA, MD
Initial Mechanical Ventilation Settings for the Intubated Asthmatic
Long B, et al. Evaluation and management of the critically ill adult asthmatic in the emergency department setting. Am J Emerg Med. 2021;44:441-51.
Category: Critical Care
Keywords: Cardiogenic Shock, Milrinone, Dobutamine (PubMed Search)
Posted: 10/28/2021 by Lucas Sjeklocha, MD
(Updated: 7/27/2024)
Click here to contact Lucas Sjeklocha, MD
Background: A cornerstone of therapy for cardiogenic shock is inotropic support with medications including dobutamine, epinephrine and milrinone. Few studies have examined these head-to-head and between dobutamine and milrinone (including only one RCT of 36 patients)
The investigators conducted a RCT of milrinone versus dobutamine for cardiogenic shock in a single quaternary care center cardiac ICU.
Inclusion: Patients over 18 with cardiogenic shock (largely clinical determination)
Exclusion: Out-of-hospital cardiac arrest, pregnancy, prior initiation of dobutamine or milrinone, or physician discretion.
Methods: 1:1 randomization stratified by affected ventricle (LV vs RV). Primary outcome was a composite of in-hospital death, resuscitated cardiac arrest, cardiac transplant, mechanical circulator support, nonfatal MI, TIA, stroke, or renal replacement therapy. Powered to detect a 20% improvement in this measure in the milrinone group (192 pts).
Results: 192 patients enrolled (96 in each arm). Average age was 70, 36% female, 90% LV dysfunction, 67% ischemic disease, 33% non-ischemic, average LVEF 25%, 68% on vasopressors. ICU admission to randomization was 23+/-92.6h for dobutamine and 17.6+/-50.6h for milrinone arms. 80% were SCAI class C shock.
Primary outcome for milrinone 49% versus dobutamine 54%, HR 0.9(0.69-1.19), p=0.47, death was the primary driver of the composite (37% vs 43%). Arrythmia requiring intervention was not different between groups (50% vs 46%). No difference in a host of other endpoints including AKI (92% vs 90%), RRT (22% vs 17%), HR, lactate, MAP, UOP, and creatinine.
Discussion: No significant differences observed in outcomes for patients with cardiogenic shock randomized to milrinone versus dobutamine. The trial addressed an important clinical question for management of cardiogenic shock and relied largely on clinical diagnosis for inclusion and likely reflected a somewhat broad range of patients. The trial was too small given observed treatment effects and few patients with RV failure. Notably, similar rates of adverse events observed in each group.
Many limitations for practice including a single specialized ICU setting, limited information on events leading to ICU admission including invasive or medical interventions during the index visit and no long term follow-up. Time to randomization, exclusion of cardiac arrest, and lack of reporting pre-ICU setting (ED, floor, cath lab) also significantly limits utility in an emergency setting.
Bottom Line: 192 patient single-center cardiac ICU-based trial shows no difference in composite or secondary endpoints between milrinone and dobutamine for cardiogenic shock, adds to a body of very limited RCTs comparing inotropes in cardiogenic shock but provides no practice changing evidence.
Mathew R, et al. Milrinone as Compared with Dobutamine in the Treatment of Cardiogenic Shock. N Engl J Med. 2021 Aug 5.
DOI: 10.1056/NEJMoa2026845
Category: Critical Care
Keywords: decompensated heart failure, hypertonic saline, furosemide (PubMed Search)
Posted: 10/19/2021 by Quincy Tran, MD, PhD
(Updated: 7/27/2024)
Click here to contact Quincy Tran, MD, PhD
Settings & Designs: a meta-analysis of 11 randomized controlled trials among patients with fluid overload.
Patients: This meta-analysis included 2987 patients with acute decompensated heart failure.
Intervention: intravenous hypertonic saline + intravenous furosemide.
Comparison: intravenous furosemide
Outcome: all-cause mortality, hospital length of stay
Study Results:
· Hypertonic saline + furosemide treatment was associated with lower relative risk of mortality (RR 0.55, 95% CI 0.33-0.76%, P< 0.05, I-square = 12%).
· Hypertonic saline + furosemide treatment was also associated with 3.8 shorter hospital length of stay (mean difference = -3.38 days, 95% CI -4.1 to -2.4, P< 0.05, I-square = 93%).
· Sodium creatine also decreased about 0.46 mg/dl (mean difference, -0.46, 95% CI -051, -0.41, P<0.05, I-square 89%) for patients received both hypertonic saline and furosemide.
Discussion:
· Most studies only included patients with advanced heart failure (NYHA class IV, EF < 35%)
· For these patients with advanced heart failure, most studies infused 150 ml of 1.5%-3% saline. However, all studies used very high doses of furosemide (500mg -1000mg BID).
Conclusion:
In patients with acute decompensated heart failure, a combination of hypertonic saline and intravenous furosemide was associated with improved outcomes, compared with a single therapy of furosemide.
Liu, Chang PhD, MD; Peng, Zhiyong PhD, MD; Gao, Xiaolan MD; Gajic, Ognjen MD; Dong, Yue MD; Prokop, Larry J. MLS; Murad, M. Hassan MD; Kashani, Kianoush B. MD, MSc, FASN, FCCP; Domecq, Juan Pablo MD. Simultaneous Use of Hypertonic Saline and IV Furosemide for Fluid Overload: A Systematic Review and Meta-Analysis, Critical Care Medicine: November 2021 - Volume 49 - Issue 11 - p e1163-e1175 doi: 10.1097/CCM.0000000000005174.
Category: Critical Care
Posted: 9/28/2021 by Duyen Tran, MD
Click here to contact Duyen Tran, MD
Intubation considerations
Vent management strategies
Laher AE, Buchanan SK. Mechanically Ventilating the Severe Asthmatic. Journal of Intensive Care Medicine. 2018;33(9):491-501.
Category: Critical Care
Posted: 9/7/2021 by Mike Winters, MBA, MD
Click here to contact Mike Winters, MBA, MD
Management of Intermediate-High Risk PE Patients
Weinstein T, et al. Advanced management of intermediate-high risk pulmonary embolism. Crit Care. 2021; 25:311.
Category: Critical Care
Posted: 8/31/2021 by Lucas Sjeklocha, MD
Click here to contact Lucas Sjeklocha, MD
Background: Interest in moving to balanced fluid administration has grown after publication of the SPLIT trial and SALT-ED/SMART trials, which showed respectively evidence of benefit to balanced crystalloid over normal saline on mortality and major adverse kidney events at 30 days.
Population/Intervention: The BaSICs trial is an RCT in 75 ICUs in Brazil, testing P-Lyte versus NS (with each arm getting two different infusion rates that were analyzed as a separate trial) for volume administration per protocol.
--10,520 ICU patients requiring fluid expansion, expected ICU stay >1 day, and 1 additional risk factor for AKI (age>65, hypotension, sepsis, MV, NIV, oliguria, elevated creatinine, cirrhosis, or acute liver failure).
--Exclusions: severe dysnatremia, expected RRT within 6 hours, expected death.
--Average age was 61, with a SOFA score of 4, and 48% on were elective surgical admissions.
Outcome:
--No difference in 90 days mortality (P-Lyte 26.4% v NS 27.2, aHR p=0.47), AKI or RRT out to 7-days, or in duration of MV, ICU LOS or hospital LOS
--Median study fluid by day 3 was 2.9L in each group
--Higher neurological SOFA score observed in P-Lyte group
--Higher mortality seen with P-Lyte in TBI subgroup (P-Lyte 31.3% vs NS 21.1%, p=0.02)
Discussion:
--Adds contrasting negative data to previous large positive RCTs showing benefit of balanaced fluids
--Expect further reanalysis/metanalysis of BSS versus NS trials
--Signal for harm in TBI pts with P-Lyte correlates with SMART point estimates that were not significant
--Compared to SMART trial population BaSICs had: 2x higher mortality, more planned surgery, received about 1L more study fluid in the first 3ds
Takeaway:
--Balanced crystalloid versus normal saline debate will continue considering this large negative trial
--Signal for possible harm in TBI population with balanced crystalloids compared to normal saline
References:
Category: Critical Care
Keywords: SOFA, sepsis, oxygen saturation (PubMed Search)
Posted: 8/25/2021 by Quincy Tran, MD, PhD
(Updated: 7/27/2024)
Click here to contact Quincy Tran, MD, PhD
Background: SOFA score has been used as a predictor for poor outcomes in patients with sepsis. However, the original SOFA score utilizes PaO2/FiO2 ratio to calculate the SOFA’s respiratory component. When there are no ABG, thus no PaO2, we have to convert patients’ spO2 to PaO2, and the amount of oxygen support to FiO2 (for example, 2 liters of oxygen via nasal cannula = 0.27). This is cumbersome.
Objective: This study assessed whether spO2 can be used instead of PaO2/FiO2 ratio for SOFA’s respiratory score.
Settings: 8 hospitals across Sweden and Canada
Patients: Adults with sepsis. 19396 patients were included for the derivation group while there were 10586 patients for the validation cohort.
Study Results:
Discussion:
Valik JK, Mellhammar L, Sundén-Cullberg J, Ward L, Unge C, Dalianis H, Henriksson A, Strålin K, Linder A, Nauclér P. Peripheral Oxygen Saturation Facilitates Assessment of Respiratory Dysfunction in the Sequential Organ Failure Assessment Score With Implications for the Sepsis-3 Criteria. Crit Care Med. 2021 Aug 18. doi: 10.1097/CCM.0000000000005318. Epub ahead of print. PMID: 34406170.
Category: Critical Care
Keywords: IVF, intravenous fluids, resuscitation, infusion rates (PubMed Search)
Posted: 8/18/2021 by Kami Windsor, MD
Click here to contact Kami Windsor, MD
Background:
There are also no clear guidelines regarding how fast fluid boluses should be administered, and there has been debate about whether different infusion rates could lead to different outcomes in patients receiving intravenous fluid (IVF) boluses (i.e. fast infusions may cause more third spacing due to the rapidity of the expansion of the intravascular space compared to fluid administered more slowly). A recent study compared IVF infusion rates in ICU patients.
-- Unblinded, randomized
-- 10,520 patients clinically requiring a fluid challenge, from 75 ICUs in Brazil
-- Infusion rate 333 mL/hr vs 999 mL/hr
* (Trial also compared plasmalyte vs 0.9% saline, analyzed in separate study)
-- Some notable exclusion criteria: severe hypo/hypernatremia, AKI or expected to need RRT 6 hrs after admission
--Other caveats:
* Faster infusion rates allowed at physician discretion in patients with active bleeding or severe hypotension (SBP < 80 or MAP < 50 mmHg); patient was returned to assigned rate after condition resolved
* Almost 1/2 the patients received at least 1L of IVF in 24 hours prior to enrollment
-- Results: No sig difference in 90-day survival, use of RRT, AKI, mechanical ventilator free days, ICU/hospital mortality/LOS
Bottom Line: There is not yet compelling evidence that there are differences in patient outcomes in patients receiving fluid boluses given at 333 cc/hr vs. 999 cc/hr.
1. Zampieri FG, Machado FR, Biondi RS, et al. Effect of slower vs faster intravenous fluid bolus rates on mortality in critically ill patients: the basics randomized clinical trial. JAMA. Published online August 10, 2021.doi:10.1001/jama.2021.11444
2. Zampieri FG, Machado FR, Biondi RS, et al. Effect of intravenous fluid treatment with a balanced solution vs 0. 9% saline solution on mortality in critically ill patients: the basics randomized clinical trial. JAMA. Published online August 10, 2021.
Category: Critical Care
Keywords: cardiac arrest, IHCA, resuscitation, epinephrine, pediatrics (PubMed Search)
Posted: 8/11/2021 by Kami Windsor, MD
Click here to contact Kami Windsor, MD
Approximately 15,000 children experience an in hospital cardiac arrest (IHCA) with little improvement in outcomes over the last two decades. During that time, epinephrine has been the constant basis for resuscitation of these patients. Current recommendations by the AHA recommend bolus dosing of epinephrine every 3-5 minutes in a pediatric cardiac arrest. Animal studies suggest that more frequent dosing of epinephrine may be beneficial.
This was a retrospective study of 125 pediatric IHCAs with 33 receiving “frequent epinephrine” interval (≤2 minutes). Pediatric CPC score 1-2 or no change from baseline was used as primary outcome to reflect favorable neurologic outcome, with frequent dosing associated with better outcome (aOR 2.56, 95%CI 1.07 to 6.14). Change in diastolic blood pressure was greater after the second dose of epinephrine among patients who received frequent epinephrine (median [IQR] 6.3 [4.1, 16.9] vs. 0.13 [-2.3, 1.9] mmHg, p=0.034).
This study is subject to all sorts of confounding and should be studied more rigorously, but suggests that more frequent dosing for pediatric IHCA may be of benefit.
Kienzle MF, Morgan RW, Faerber JA, et al. The Effect of Epinephrine Dosing Intervals on Outcomes from Pediatric In-Hospital Cardiac Arrest. Am J Respir Crit Care Med. 2021. doi: 10.1164/rccm.202012-4437OC.
Category: Critical Care
Keywords: Modified Clamshell thoracotomy, resuscitative thoracotomy, randomized control trial (PubMed Search)
Posted: 8/3/2021 by Kim Boswell, MD
Click here to contact Kim Boswell, MD
Resuscitative thoracotomy is a dramatic and heroic procedure used in the emergency department in an attempt to resuscitate a patient in arrest due to trauma. There are a few techniques commonly used, but due to the extreme nature of the procedure no prior randomized controlled trials (RCTs) have been done.
The modified clamshell thoracotomy (MCT) is a technique in which the standard left anterolateral thoracotomy (LAT) is extended across the sternum, but does not involve surgical opening of the right chest. The MCT allows for increased visualization of the mediastinum and thoracic cavity structures.
Sixteen Emergency trained physicians (approximately half attending and half senior residents) from a level 1 trauma center underwent didactic and skill based training on both the MCT and LAT techniques using fresh, human cadavers. Following training they were randomized based on order of intervention, performing both techniques.
Their thoracotomies were assessed by a board certified surgeon and “success” was determined based on the complete delivery of the heart and cross clamping of the descending aorta.
Primary outcome: time to successful completion of procedure
Secondary outcomes: successful delivery of the heart from the pericardial sac (as well as time to delivery), cross clamping of the aorta (and time to clamping), procedural completion and number of iatrogenic injuries.
Overall, there was no statistical difference in primary outcome or successful completion between the MCT compared to the LAT (67% vs. 40%). However, 100% of the LAT resulted in some form of iatrogenic injury (rib fractures, lacerations of the diaphragm,/esophagus/heart/lung) compared to 67% of the MCT technique. There was no associated difference in success when previous experience (attending vs. senior resident) were compared. Lastly, MCT was the favored technique of the majority of the study subjects.
Prospective Randomized Trial of Standard Left Anterolateral Thoracotomy Versus Modified Bilateral Clamshell Thoracotomy Performed by Emergency Physicians. Ann Emerg Med. 2021 Mar;77(3):317-326 doi: 10.1016/j.annemergmed.2020.05.042nnemergmed.2020.05.042Prospective Randomized Trial of Standard Left Anterolateral Thoracotomy Versus Modified BiProspective Randomized Trial of Standard Left Anterolateral Thoracotomy Versus Modified Bilateral Clamshell Thoracotomy Performed by Emergency Physicians. Ann Emerg Med. 2021 Mar;77(3):317-326 doi: 10.1016/j.annemergmed.2020.05.042lateral Clamshell Thoracotomy Performed by Emergency Physicians. Ann Emerg Med. 2021 Mar;77(3):317-326 doi: 10.1016/j.annemergmed.2020.05.042
Category: Critical Care
Keywords: COVID-19, Antiviral, Hydroxychloroquine (PubMed Search)
Posted: 7/27/2021 by Mark Sutherland, MD
(Updated: 7/27/2024)
Click here to contact Mark Sutherland, MD
The much anticipated REMAP-CAP trial was epublished ahead of print July 12th in Intensive Care Medicine. It was an RCT investigating four antiviral strategies in critically ill adults with COVID-19: lopinavir-ritonavir, hydroxychloroquine, a combination of the two, and no antiviral therapy (control group).
Despite the hype around protease inhibitors, hydroxychloroquine, and other unproven therapies in COVID (lookin at you next, Ivermectin...), all three strategies had WORSE outcomes than placebo. They all decreased organ-support-free days (all reaching statistical significance), which was the primary outcome. They also all led to longer ICU time, longer time to hospital discharge, and reduced 90 day survival. Not only does this study show no benefit, it shows fairly convincing signs of harm to these therapies.
Bottom Line: Protease inhibitors (e.g. lopinavir-ritonavir) and hydroxychloroquine are unproven therapies for critical COVID-19 infection, and are not recommended. Providers should focus on interventions with demonstrated benefit, most notably steroids and good supportive/critical care.
Arabi YM, Gordon AC, Derde LPG, Nichol AD, Murthy S, Beidh FA, Annane D, Swaidan LA, Beane A, Beasley R, Berry LR, Bhimani Z, Bonten MJM, Bradbury CA, Brunkhorst FM, Buxton M, Buzgau A, Cheng A, De Jong M, Detry MA, Duffy EJ, Estcourt LJ, Fitzgerald M, Fowler R, Girard TD, Goligher EC, Goossens H, Haniffa R, Higgins AM, Hills TE, Horvat CM, Huang DT, King AJ, Lamontagne F, Lawler PR, Lewis R, Linstrum K, Litton E, Lorenzi E, Malakouti S, McAuley DF, McGlothlin A, Mcguinness S, McVerry BJ, Montgomery SK, Morpeth SC, Mouncey PR, Orr K, Parke R, Parker JC, Patanwala AE, Rowan KM, Santos MS, Saunders CT, Seymour CW, Shankar-Hari M, Tong SYC, Turgeon AF, Turner AM, Van de Veerdonk FL, Zarychanski R, Green C, Berry S, Marshall JC, McArthur C, Angus DC, Webb SA; REMAP-CAP Investigators. Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial. Intensive Care Med. 2021 Aug;47(8):867-886. doi: 10.1007/s00134-021-06448-5. Epub 2021 Jul 12. PMID: 34251506; PMCID: PMC8274471.
Category: Critical Care
Posted: 7/20/2021 by Mike Winters, MBA, MD
(Updated: 7/27/2024)
Click here to contact Mike Winters, MBA, MD
Hemophagocytic Lymphohistiocytosis (HLH)
Morrissette K, et al. Hemophagocytic lymphohistiocytosis in the emergency department: recognizing and evaluating a hidden threat. J Emerg Med. 2021;60:743-751.