Thiele H, Akin I, Sandri M, Fuernau G, De Waha S, Meyer-Saraei R, et al. PCI Strategies in Patients with Acute Myocardial Infarction and Cardiogenic Shock. N Engl J Med. 2017 Dec 21;377(25):2419–32. Introduction Cardiogenic shock following acute myocardial infarction carries high mortality; besides, long-term outcomes remain poor among survivors (1). The SHOCK trial, the first… Continue reading Trailblazers: Culprit lesion alone or multivessel PCI in myocardial infarction with cardiogenic shock? The CULPRIT-SHOCK trial
Casaer MP, Mesotten D, Hermans G, Wouters PJ, Schetz M, Meyfroidt G, et al. Early versus Late Parenteral Nutrition in Critically Ill Adults. N Engl J Med. 2011 Aug 11;365(6):506–17. Introduction The concept of intravenous nutrition arose during World War I with the introduction of sterile glucose solutions in water (1). A decade later, intravenous protein… Continue reading The EPaNIC trial: Early versus Late Parenteral Nutrition in Critically Ill Adults
Acute Respiratory Distress Syndrome Network, Brower RG, Matthay MA, et al. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342(18):1301-1308 Introduction In the early days of mechanical ventilation, the primary aim was to normalize arterial blood gases. Little was… Continue reading Critical Care Trailblazers: The ARDSnet trial of low tidal volume ventilation
Thiele, Holger et al. “Extracorporeal Life Support in Infarct-Related Cardiogenic Shock.” The New England journal of medicine vol. 389,14 (2023): 1286-1297. doi:10.1056/NEJMoa2307227 Background Acute myocardial infarction is complicated by cardiogenic shock in approximately 10% of patients (1). Despite timely revascularization, the mortality remains high, around 40–50% (2). Mechanical support, especially veno-arterial extracorporeal membrane oxygenation, has been increasingly… Continue reading Veno-arterial ECMO in cardiogenic shock following acute MI: The ECLS-SHOCK trial
Mismetti P, Laporte S, Pellerin O, Ennezat PV, Couturaud F, Elias A, et al. Effect of a Retrievable Inferior Vena Cava Filter Plus Anticoagulation vs Anticoagulation Alone on Risk of Recurrent Pulmonary Embolism: A Randomized Clinical Trial. JAMA. 2015 Apr 28;313(16):1627 Introduction More than half a century ago, Kazi Mobin-Uddin et al. reported the use… Continue reading Trailblazers: Retrievable IVC Filter Plus Anticoagulation vs. Anticoagulation Alone on Risk of Recurrent Pulmonary Embolism – The PREPIC 2 trial
Molyneux, Andrew et al. “International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomized trial.” Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association vol. 11,6 (2002): 304-14 Introduction Intracranial aneurysms occur in about 5–8% of the population (1). Aneurysmal rupture often leads… Continue reading Trailblazers: Clipping vs. coiling of intracranial aneurysms – the ISAT trial
Jüttler E, Unterberg A, Woitzik J, Bösel J, Amiri H, Sakowitz OW, et al. Hemicraniectomy in Older Patients with Extensive Middle-Cerebral-Artery Stroke. N Engl J Med. 2014 Mar 20;370(12):1091–100. Introduction Massive hemispheric involvement occurs in up to 10% of patients with supratentorial infarcts (1). Life-threatening cerebral edema often follows, referred to as malignant middle-cerebral-artery syndrome (2), with… Continue reading Trailblazers: hemicraniectomy in ischemic stroke for older patients – the DESTINY II trial
Introduction Endovascular therapy for acute ischemic stroke was investigated more than two decades ago, especially among patients with large or more proximal occlusion. Conventional intravenous thrombolysis among patients with large, proximal occlusions may not be efficacious and carries the risk of fatal intracranial hemorrhage. The PROACT trials of the late 1990s evaluated the use of… Continue reading Trailblazers: Mechanical thrombectomy at 6–24 hours after stroke – the DAWN trial
Introduction Acute ischemic stroke remains one of the few neurological disorders in which expeditious diagnosis and treatment could potentially lead to complete recovery. In 1995, the National Institute of Neurological Disorders and Stroke (NINDS) study group published their landmark randomized controlled trial (RCT) of intravenous thrombolysis with alteplase compared to placebo in acute… Continue reading Trailblazers: Extended time window for thrombolysis in stroke – the ECASS III trial
Andersen HR, Nielsen TT, Rasmussen K, et al. The DANAMI-2 Investigators. A comparison of coronary angioplasty with fibrinolytic therapy in acute myocardial infarction. N Engl J Med. 2003 Aug 21;349(8):733-42. doi: 10.1056/NEJMoa025142. PMID: 12930925. Introduction In September 1977, a 38-year-old man presented to the University Hospital in Zurich, Switzerland, with myocardial infarction. The likely culprit… Continue reading Trailblazers: On-site Fibrinolysis vs. Transfer for angioplasty in STEMI – The DANAMI II Trial
Annane D, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002 Aug 21;288(7):862-71 Introduction and background Historically, clinicians were often beguiled by the potent anti-inflammatory effect of corticosteroids and their putative benefits in septic patients. In the summer of 1976, William Schumer presented… Continue reading Critical Care Trailblazers: Low-dose Corticosteroids in Septic Shock
Monti G, Bradic N, Marzaroli M, Konkayev A, Fominskiy E, Kotani Y, et al. Continuous vs Intermittent Meropenem Administration in Critically Ill Patients With Sepsis: The MERCY Randomized Clinical Trial. JAMA. 2023 Jul 11;330(2):141–51. Background The efficacy of beta-lactam antibiotics is related to the duration for which drug levels remain above the minimum inhibitory concentration… Continue reading Journal review: Continuous vs. intermittent dosing of meropenem – The MERCY trial
Kumar A et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006 Jun;34(6):1589–96. Introduction In the summer of 1928, Alexander Fleming, on his return from holidays, was disconcerted by a mold that had contaminated his Petri dishes. On examination… Continue reading Critical Care Trailblazers: Early Antibiotics in Septic Shock
PATCH-Trauma Investigators and the ANZICS Clinical Trials Group; Gruen RL, Mitra B, Bernard SA, et al. Prehospital Tranexamic Acid for Severe Trauma. N Engl J Med. 2023 Jun 14. doi: 10.1056/NEJMoa2215457. Epub ahead of print. PMID: 37314244. Introduction Continued hemorrhage is a leading cause of preventable deaths in patients with severe trauma. Exacerbation of the… Continue reading Prehospital Tranexamic Acid for Severe Trauma – The PATCH trial
Introduction Internal cardiac massage was employed to resuscitate the arrested heart from the late 19th century. This technique was largely confined to intraoperative cardiac arrest in anesthetized patients. If the abdomen was open, the surgeon would attempt subdiaphragmatic compression, a technique later found to be largely ineffective. Hence, if spontaneous cardiac activity did not occur,… Continue reading Trailblazers: Compression-Only CPR in Out-of-Hospital Cardiac Arrest – The DART Trial
Hutchinson PJ, et al. The RESCUE-ASDH Trial Collaborators. Decompressive Craniectomy versus Craniotomy for Acute Subdural Hematoma. N Engl J Med. 2023 Jun 15;388(24):2219-2229 Introduction Acute subdural hematomas occur in nearly two-thirds of patients with traumatic brain injury and are associated with poor functional recovery and relatively high mortality (1). An acute subdural hematoma is evacuated through a… Continue reading Decompressive Craniectomy versus Craniotomy for Acute Subdural Hematoma
Introduction In 1960, Nils Lundberg, a Swedish neurosurgeon, measured the intraventricular pressure (ICP) in 64 patients (1). He inserted a plastic catheter into the frontal horn of the lateral ventricle and connected it to a strain gauge pressure transducer. Recording was carried out with an ink-writing potentiometer. Although archaic by modern standards, he used this equipment… Continue reading Critical Care Trailblazers: ICP monitoring and the BEST-TRIP trial
Introduction Uncontrolled blood glucose levels have been associated with poor clinical outcomes among critically ill patients. Stress-related release of counterregulatory hormones, including catecholamines, corticosteroids, and glucagon tend to increase blood glucose levels in critical illness (1). Hyperglycemia may lead to harm through cytokine release and generation of reactive oxygen species (2). Furthermore, it may impair the bactericidal… Continue reading Critical Care Trailblazers: The NICE-SUGAR trial
Introduction In the late 19th century, physiologists were fascinated by the movement of fluid between the intravascular and interstitial compartments and its effect on the circulating volume. Ernest Starling, working from his laboratory at Guy’s Hospital in London, proposed that the net transudation of fluid depends on two forces. The capillary pressure tends to drive fluid… Continue reading Critical Care Trailblazers: The CHEST Trial
Platelet Transfusion before CVC Placement in Patients with Thrombocytopenia (the PACER trial) Van Baarle FLF, Van De Weerdt EK, Van Der Velden WJFM, Ruiterkamp RA, Tuinman PR, Ypma PF, et al. Platelet Transfusion before CVC Placement in Patients with Thrombocytopenia. N Engl J Med. 2023 May 25;388(21):1956–65. Background The risk of major bleeding complications associated… Continue reading Do you need prophylactic platelets before CVC insertion in thrombocytopenic patients?
Introduction Back in the 1950s, in war-torn Japan, a husband-and-wife team of researchers, Shosuke and Utako Okamoto were scripting medical history. They were passionately focused on identifying an antagonist of clot breakdown that might arrest severe hemorrhage. Exsanguinating postpartum hemorrhage was a leading cause of maternal mortality in Japan during this period. They realized that… Continue reading Critical Care Trailblazers: The CRASH-2 trial
The concept of the floatation catheter On a bright autumn afternoon of 1967, Jeremy Swan stood by the beach at Santa Monica, watching sailboats pass by. He was a cardiologist at the Cedars of Lebanon Hospital, Los Angeles, and had taken time off following a particularly difficult cardiac catheterization just a few days ago. As… Continue reading Critical Care Trailblazers: The PAC-Man Trial
Peek GJ, Mugford M, Tiruvoipati R, Wilson A, Allen E, Thalanany MM, et al. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet. 2009 Oct 17;374(9698):1351–63. Introduction By the turn of the millennium, refinements in ventilation strategies, including the use… Continue reading Critical Care Trailblazers: The CESAR Trial
De Backer D, Biston P, Devriendt J, Madl C et al; SOAP II Investigators. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med. 2010 Mar 4;362(9):779-89 Introduction Acute circulatory failure may be of varied etiology and carries a high mortality without expeditious evaluation and timely management. One of the basic… Continue reading Critical Care Trailblazers: The SOAP II trial
Thiele H, Zeymer U, Neumann FJ, Ferenc M, Olbrich HG, Hausleiter J, et al. Intraaortic Balloon Support for Myocardial Infarction with Cardiogenic Shock. N Engl J Med. 2012 Oct 4;367(14):1287–96. Introduction The concept of diastolic augmentation of coronary blood flow in patients with left ventricular failure arose in the 1950s. Animal experimenters attempted wrapping of… Continue reading Critical Care Trailblazers: The IABP-SHOCK II trial
Hernández G, et al. Effect of post-extubation noninvasive ventilation with active humidification vs high-flow nasal cannula on reintubation in patients at very high risk for extubation failure: a randomized trial. Intensive Care Med. 2022 Dec;48(12):1751–9. Background Both non-invasive ventilation (NIV) and high-flow nasal cannula (HFNC) have been used solely and in combination as respiratory support… Continue reading How does NIV with active humidification compare with HFNC among patients at high risk of extubation failure?
Vinsonneau C, Camus C, Combes A, et al. The Hemodiafe Study Group. Continuous venovenous haemodiafiltration versus intermittent haemodialysis for acute renal failure in patients with multiple-organ dysfunction syndrome: a multicentre randomised trial. Lancet. 2006 Jul 29;368(9533):379-85 Introduction Until the early 1980s, intermittent hemodialysis (IHD) was the standard modality of renal replacement therapy (RRT) in critically… Continue reading Critical Care Trailblazers: The Hemodiafe Trial and the Modality of Renal Replacement Therapy
Introduction and background Nearly 60 years ago, early experimental studies on the hemodynamic and renal effects of dopamine were carried out by investigators at the Emory University, in Atlanta. In 1963, Goldberg and his co-investigators from this group published the results of a study that evaluated the effect of dopamine infusion in four patients with… Continue reading Critical Care Trailblazers: The ANZICS Dopamine Trial
Dequin et al. N Engl J Med. 2023 Mar 21 Background Corticosteroids exert powerful anti-inflammatory and immunomodulatory properties that may attenuate the consequences of severe community-acquired pneumonia (CAP), and thereby, improve clinical outcomes. Although many randomized controlled trials (RCTs) have been carried out to evaluate the potential beneficial effect of corticosteroids in CAP, reduced mortality… Continue reading The CAPE-COD trial: Hydrocortisone in Severe Community-Acquired Pneumonia
Kress JP, Pohlman AS, O'Connor MF, Hall JB. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med. 2000 May 18;342(20):1471-7 Introduction Dating back to the 1980s, sedative agents were increasingly used to improve patient comfort during mechanical ventilation. The practice evolved over time with the nearly routine use… Continue reading Critical Care Trailblazers: Daily Sedation Interruption in Ventilated Patients
Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001 Nov 8;345(19):1368-77. Introduction There was no standardized approach to the early management of severe sepsis and septic… Continue reading Critical Care Trailblazers: Early Goal-Directed Therapy (EGDT) in Severe Sepsis and Septic Shock
Introduction Historically, surgical decompression was employed as a desperate measure to reduce pressure within the skull in life-threatening brain injury. At the turn of the 20th century, Theodor Kocher (Fig. 1) first proposed the potential of decompressive craniotomy to reduce intracranial pressure (ICP) in patients with traumatic brain injury (TBI). In 1901, he wrote that favorable… Continue reading Critical care trailblazers: the DECRA trial
Suverein MM, Delnoij TSR, Lorusso R, et al. Early Extracorporeal CPR for Refractory Out-of-Hospital Cardiac Arrest. N Engl J Med. 2023 Jan 26;388(4):299-309 Background In refractory cardiac arrest, the addition of extracorporeal membrane oxygenation to conventional cardiopulmonary life support (e-CPR) may help maintain organ perfusion and alleviate neurological damage. Besides, it offers a window of… Continue reading Early Extracorporeal CPR for Refractory Out-of-Hospital Cardiac Arrest
Introduction Neuromuscular blockade has been in routine practice in anesthesia and critical care for more than half a century. Claude Bernard, one of the pioneer researchers on neuromuscular blocking agents, conducted groundbreaking animal experiments on the effect of curare in the 19th century. He watched with interest and intrigue as curare administration instantly abolished convulsions arising… Continue reading Critical Care Trailblazers: the ACURASYS Trial
Bickell WH, Wall MJ, Pepe PE, Martin RR, Ginger VF, Allen MK, et al. Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries. N Engl J Med. 1994 Oct 27;331(17):1105–9. Introduction Early, aggressive fluid administration was long considered to be the key to the resuscitation of patients who suffered major hemorrhage following… Continue reading Critical Care Trailblazers: delayed resuscitation in trauma
National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Clinical Trials Network; Shapiro NI, Douglas IS, Brower RG, et al. Early Restrictive or Liberal Fluid Management for Sepsis-Induced Hypotension. N Engl J Med. 2023 Jan 21. doi: 10.1056/NEJMoa2212663. Epub ahead of print. PMID: 36688507. Background Fluid resuscitation is one… Continue reading Early Restrictive or Liberal Fluid Management for Sepsis-Induced Hypotension (The CLOVERS trial)
Introduction More than half a century ago, it was well-known that ventilation of the dependent lung might be impaired in mechanically ventilated patients. Children with cystic fibrosis could expectorate thick, tenacious secretions characteristic of the disease by positioning themselves on their hands and knees. Quite often, such positioning also enabled them to breathe easier (1). Based… Continue reading Critical care trailblazers: the PROSEVA trial – a turn for the better
Historical background Tracheostomy appears to have been in practice as a life-saving intervention to relieve upper airway obstruction for more than 2,000 years. Descriptions of a throat incision, suggestive of tracheostomy, are found in the sacred Hindu text, the Rig Veda, that dates back to 1500 BCE (1). Alexander the Great, the King of Macedonia who lived between… Continue reading Critical care trailblazers: early vs. late tracheostomy – the TracMan trial
Introduction Transfusion of blood was first reported in the early 19th century. In the early days of transfusion history, direct donor-to-recipient transfusion was commonly practiced. By 1914, the addition of citrate was found to prevent clotting, thus opening the door to the storage of collected blood. As World War I broke out in Europe, there was… Continue reading Critical care trailblazers: transfusion thresholds in critical care – the TRICC trial
Cheskes S, Verbeek PR, Drennan IR, et al. Defibrillation Strategies for Refractory Ventricular Fibrillation. N Engl J Med. 2022 Nov 24;387(21):1947-1956. doi: 10.1056/NEJMoa2207304. Epub 2022 Nov 6. PMID: 36342151. Background Double sequential (DSED) and vector change (VC) defibrillation have been in use for many years. In observational studies and case reports, these strategies have been… Continue reading Alternate defibrillation strategies for refractory ventricular fibrillation
Introduction Cooling down the body as a therapeutic modality has been prevalent since ancient times. The Edwin Smith Papyrus (Fig. 1), an Egyptian medical treatise dating back to 3,500 B.C.E, describes the use of hypothermia as a treatment for various ailments (1). Temple Fay reinvigorated interest in hypothermia in modern-day practice in the 1930s with his… Continue reading Critical care trailblazers: therapeutic hypothermia after cardiac arrest – the HACA trial
TEAM Study Investigators and the ANZICS Clinical Trials Group, Hodgson CL, Bailey M, Bellomo R, Brickell K, Broadley T, et al. Early Active Mobilization during Mechanical Ventilation in the ICU. N Engl J Med. 2022 Nov 10;387(19):1747-1758. doi: 10.1056/NEJMoa2209083. Epub 2022 Oct 26. PMID: 36286256. Population and setting The study was held from February 27,… Continue reading Early mobilization of mechanically ventilated patients: the TEAM trial
Introduction Albumin, along with hemoglobin and fibrin, were among the first proteins to be identified in the human body. Considering the putative benefits including maintenance of colloid osmotic pressure and more efficient filling of the intravascular compartment, it evolved into an effective resuscitation fluid. Widespread use followed the initial introduction into clinical practice in the… Continue reading Trailblazers: how albumin was proven to be safe
Connors AF, Speroff T, Dawson NV, Thomas C, Harrell FE, Wagner D, et al. The effectiveness of right heart catheterization in the initial care of critically ill patients. SUPPORT Investigators. JAMA. 1996 Sep 18;276(11):889–97. Introduction The utility of the pulmonary artery catheter in critically ill patients has been shrouded in controversy ever since its introduction… Continue reading Trailblazers in critical care: the rise and fall of the pulmonary artery catheter
PEEP: the early beginnings In the 1960s, at the Colorado General Hospital, David Ashbaugh and colleagues formed a team to care for patients who required respiratory support. Among the patients who required ventilator support, they identified a few patients who remained severely hypoxic with diffuse lung infiltrates. Mortality was high among these patients; autopsy revealed… Continue reading History and evolution of mechanical ventilation: part 2
Mouth to mouth resuscitation can be historically traced back to the book of Kings in the Old Testament (1). The prophet Elisha, on seeing a little boy who appeared dead, “laid on top of the child, put his mouth to the child’s mouth, his eyes on the child’s eyes, his hands on the child’s hands,… Continue reading History and evolution of mechanical ventilation: Part I
Introduction Extracorporeal membrane oxygenation (ECMO) has been in use as rescue therapy for acute respiratory failure for more than half a century. In 1972, Hill et al. reported their experience with ECMO use in a 24 year old man who sustained transection of the thoracic aorta and multiple orthopedic injuries following a motor vehicle accident (1).… Continue reading Extracorporeal membrane oxygenation: evolution over the years
Monitoring of ventilator graphics is a crucial facet of care in mechanically ventilated patients. The information gleaned from interpretation of graphics offers pertinent information regarding the delivery of ventilation and patient-ventilator interaction. Ventilatory management based on information derived from the graphics display enables the prevention of potential complications, and thereby, improves clinical outcomes (1). A thorough knowledge… Continue reading Ventilator graphics: interpretation and optimization of mechanical ventilation
Introduction Shock is characterized by the failure of circulation to deliver adequate oxygen and nutrients to the tissues. Pharmacological support is often required to stabilize the hemodynamic status; a wide array of agents is employed by clinicians in this scenario. Although controlled trials have compared agents used for hemodynamic support, there is no robust evidence… Continue reading The choice of vasopressor in shock: current evidence
The World Health Organization reported the emergence of omicron (B.1.1.529), the fifth SARS-CoV-2 variant of concern, on 25th November 2021.1 The first report of the omicron variant was from Botswana, followed by a case from Hong Kong. A steep rise in cases was observed in South Africa, especially from the Gauteng province in the ensuing… Continue reading The omicron variant: what do we know so far?
Background Non-invasive modalities of respiratory support are increasingly being employed in the management of acute hypoxemic respiratory failure in COVID-19, considering early reports that suggested high mortality with invasive mechanical ventilation.1 Respiratory support with high-flow nasal cannula (HFNC) has been found to be associated with reduced 90-day mortality in non-COVID-19-related acute hypoxemic respiratory failure.2 In a… Continue reading High-flow nasal cannula in COVID-19: the HiFLo-Covid randomized controlled trial￼
The 2021 Surviving Sepsis Campaign guidelines for the management of sepsis and septic shock have been published.1 The guidelines continue to emphasize the importance of rapidity and appropriateness in the recognition and care of patients suspected to have sepsis. The recommendations represent an important guidepost for the busy bedside clinician in providing optimal care and… Continue reading The 2021 Surviving Sepsis Guidelines
Jose Chacko, Gagan Brar Meta-analysis of randomized controlled trials on tocilizumab in COVID-19 Snow TAC, et al. Tocilizumab in COVID-19: a meta-analysis, trial sequential analysis, and meta-regression of randomized-controlled trials. Intensive Care Med. 2021 Jun;47(6):641-652. doi: 10.1007/s00134-021-06416-z. Interleukin-6 antagonism has been one of the therapeutic approaches that have evinced interest in COVID-19 treatment. The REMAP-CAP1 and… Continue reading ICU headlines this fortnight: August 1, 2021
18–25 July 2021 Jose Chacko, Gagan Brar Death and disability after critical illness Higgins AM, et al. Predictors of death and new disability after critical illness: a multicenter prospective cohort study. Intensive Care Med. 2021;47(7):772-781 The PREDICT study was carried out to evaluate the prevalence and predictors of death or new-onset disability after critical illness.1 This… Continue reading ICU headlines this fortnight
The size of the functional lung is highly variable in acute respiratory distress syndrome (ARDS). The elastance of the respiratory system (Ers) is more likely to reflect the functional lung size compared to the predicted body weight. It indicates the degree of lung stiffness and is represented by the pressure required to inflate the lungs.… Continue reading Driving pressure: a more appropriate target compared to tidal volume in ARDS?
There is increasing worldwide experience in the management of ventilation in patients with COVID-19 associated acute respiratory distress syndrome (ARDS). Healthcare systems have been stretched to the limit with a relative lack of resources against the background of a rapid surge in patients who are critically ill. A large majority of critically ill patients with… Continue reading Invasive mechanical ventilation in COVID-19 associated ARDS
Introduction The COVID-19 pandemic has been raging for well over a year in most parts of the world. Several therapeutic agents have been employed, many based on little scientific reasoning, often dictated by desperation. After several months of research, dexamethasone emerged as a possible therapeutic modality that may improve survival in patients with severe COVID-19.… Continue reading Corticosteroids in COVID-19: is discretion the better part of valor?
The COVID-19 pandemic continues to rage unabated in many parts of the world. India is by far the worst affected, with uncontrolled transmission across the country. Mutant variants have been implicated in the second wave that has ravaged most of the states. The quest for therapeutic options continues; monoclonal antibodies have been the focus of… Continue reading Monoclonal antibodies against SARS-CoV-2: a ray of hope?
Thrombo-inflammation in COVID-19 The SARS-COV-2 virus invades endothelial cells leading to microvascular inflammation, which in turn, triggers an intense prothrombotic state, termed thrombo-inflammation. The levels of coagulation factors, including fibrinogen and factor VIII, are often elevated in COVID-19. Circulating thrombotic microparticles and hyperviscosity also contribute to the prothrombotic state. The prothrombotic state in COVID-19 appears… Continue reading Thromboprophylaxis in COVID-19: standard or enhanced dose?
ChAdOx1 nCov-19-associated vaccine-induced immune thrombotic thrombocytopenia (VITT) From February 2021 onwards, there have been several reports of unusual thrombotic phenomena associated with thrombocytopenia among subjects who received the ChAdOx1 nCov-19 vaccine. These reports led to a temporary pause in ChAdOx1 nCov-19 administration across several European countries, pending further investigation regarding a possible link. Subsequently, the… Continue reading ChAdOx1 nCov-19-associated vaccine-induced immune thrombotic thrombocytopenia (VITT)
Incidence of anemia in the ICU Anemia is all too common among critically ill patients, with 30–50% of patients receiving red cell transfusion. The etiology of anemia in the ICU is multifactorial, contributed by intravenous fluid resuscitation with the resulting hemodilution, repeated blood sampling, low erythropoietin levels induced by inflammatory cytokines, and abnormalities of iron… Continue reading Anemia and transfusion thresholds in the critically ill
Background The dysregulated host response observed in severe COVID-19 infection with the release of cytokines has been implicated as a perpetrator of poor outcomes in COVID-19. The “cytokine storm” typically leads to the release of several mediators, including interleukins, interferons, and tumor necrosis factor. Although this innate response is directed to combat and eliminate the… Continue reading Calming the cytokine storm in COVID-19: A new ray of hope?
Background The Oxford-AstraZeneca vaccine against COVID-19 infection has been approved and extensively used in several countries, including India. In contrast to the earlier recommendation to administer the primary and booster doses 4 weeks apart based on previously published randomized controlled trials, the UK has adopted an approach of administering the vaccine in two doses at… Continue reading The Oxford-AstraZeneca vaccine: What is the optimal time interval between the primary and booster doses? Would a single dose be efficacious?
Several vaccines are being employed against COVID-19 following expedited evaluation and manufacturing processes. Currently, more than 50 potential vaccines are undergoing clinical trials in various phases.1 Effective immunization is considered to be an important strategy in the control of the COVID-19 pandemic. Phases of vaccine development The conventional methodology of vaccine development involves several phases. The… Continue reading COVID-19 vaccines: updated 31st January, 2021
The beneficial effects of mechanical ventilation is closely related to the prevention of ventilator-induced lung injury (VILI). The harmful effects of positive pressure ventilation may be mitigated by the application of appropriate levels of positive end-expiratory pressure (PEEP). In their seminal paper, Ashbaugh et al. observed the beneficial effect of PEEP on arterial oxygenation in… Continue reading PEEP titration by the bedside: how do we set it right?
Non-invasive respiratory support using a high-flow nasal cannula (HFNC) is an emerging modality of therapy in patients with acute hypoxemic respiratory failure. Although widely established to be efficacious in respiratory illnesses of varying etiology leading to hypoxia, there is limited information regarding its usefulness in COVID-19 pneumonia. Concerns have been raised regarding aerosolization and transmission… Continue reading High-flow nasal cannula in COVID-19
The COVID-19 pandemic continues to cause perturbation worldwide, with healthcare systems struggling to cope with second waves and increasing incidence of newly infected patients. India may be witnessing a plateau effect, but the worst may be far from over. Today, we have a clearer understanding of effective therapeutic interventions compared to the early phase of… Continue reading Remdesivir in COVID-19: A tale of two trials
At the onset of the COVID-19 pandemic, there was a considerable lack of information regarding the pathophysiology of lung involvement, with several implausible hypotheses being proposed.1 With a better understanding of the disease, it is abundantly clear that COVID-19 related acute respiratory distress syndrome (ARDS) is characterized by diffuse alveolar damage with significant involvement of the… Continue reading Respiratory support of COVID-19: evolving strategies
Introduction Lung ultrasonography has been established to offer diagnostic capability similar to chest CT; it is more efficacious compared to chest radiography in the evaluation of pneumonia and the adult respiratory distress syndrome (ARDS). Besides, lung ultrasonography is easily carried out at the point of care, with the added advantage of repeated examination as required.… Continue reading Lung ultrasonography in COVID-19
The COVID-19 outbreak continues to surge in most parts of India, with health systems being stretched to the limit across the country. Several studies have been carried out in the past few months in the quest for therapeutic options that may have a favorable impact on clinical outcomes. Although there have been no dramatic breakthroughs,… Continue reading COVID-19 therapeutic update: September 22, 2020
The epidemiology and clinical characteristics of COVID-19 are much better understood today compared to the early stage of the pandemic several months ago. However, our knowledge of the pathophysiological changes in the lung remains largely elusive. Many patients with COVID-19 present with severe hypoxemia, yet remain remarkably comfortable, a phenomenon that has been alluded to… Continue reading COVID-19: the mystery behind “happy” hypoxemia
Critical care medicine is a relatively new area of specialization. Several landmark studies have been published over the years that have transformed the way we practice and added a new dimension to our approach to patient care. I have summarized the groundbreaking literature that has captivated our attention over the years and continues to influence… Continue reading Trailblazers in critical care: ten studies that changed the way we practice
Severe COVID-19 infection is characterized by coagulopathy, with manifestations related to arterial and venous thrombosis. Often unrecognized, lethal complications may ensue, including stroke and acute coronary syndrome. COVID-19-associated coagulopathy (CAC) is similar to, yet distinctively different, from sepsis-induced coagulopathy (SIC) and disseminated intravascular coagulation (DIC). There are several reports of sudden, out-of-hospital deaths associated with… Continue reading COVID-19 associated coagulopathy: more questions than answers?
The cytokine storm, arising from a dysregulated host response, has captivated mainstream and scientific media in recent times with its possible role leading to poor outcomes in COVID-19. It is characterized by the release of mediators, including chemokines, interleukins, interferons, and tumor necrosis factors. This innate response that commonly occurs in bacterial and viral infections… Continue reading Weathering the storm of COVID-19: the role of cytokine inhibitors
An intense inflammatory response is often seen in patients with COVID-19 infection leading to multiorgan dysfunction, including lung injury and severe acute respiratory distress syndrome (ARDS). Complement pathways are activated, resulting in microvascular injury and a procoagulant state.1 The hyperinflammatory response in COVID-19 may resemble secondary hemophagocytic lymphohistiocytosis (sHLH), characterized by high levels of C-reactive protein,… Continue reading Corticosteroids in COVID-19: A ray of light at the end of a dark tunnel?
There is ongoing search for effective therapies in COVID-19 infection in the face of the unabated spread of the disease in several countries, including India. Considering the lack of a vaccine and therapeutic breakthroughs, several drugs already in use for other diseases are being investigated and repurposed for use in COVID-19 infection. Recently, there have… Continue reading COVID-19: update on therapeutic options
The acute respiratory distress syndrome (ARDS), characterized by hypoxemia and bilateral alveolar infiltrates, was described in 1967 by Ashbaugh et al.1 Ventilation strategies in ARDS have undergone considerable refinement over the years. A lung-protective ventilation strategy using low tidal volumes may be one of the key interventions to reduce ventilator-induced lung injury (VILI).2 Beneficial effects of… Continue reading Neuromuscular blocking agents in severe acute respiratory distress syndrome: benefit or harm?
The physiological benefits and improvement in clinical outcomes with prone ventilation are well established in patients who are intubated and mechanically ventilated (1). Would the favorable physiological effects of the prone position benefit non-intubated, spontaneously breathing patients with acute hypoxemic respiratory failure? In light of an increasing number of patients with COVID-19 pneumonia and constrained healthcare… Continue reading Awake proning in non-intubated patients
The COVID-19 pandemic continues to wreak death and devastation across most parts of the world. The curve may have flattened in many parts of Europe, but the worst may not yet be over for the US. We are still unclear about the trajectory in India. In the meantime, theories abound regarding mechanisms of causation of… Continue reading COVID-19 update: April 24, 2020
The COVID-19 pandemic has spread to 210 countries, affecting approximately 1.7 million people and resulting in more than 103,000 deaths until now. More than one-third of the world population, including India, is currently in lockdown. Although the epidemic curve has flattened in some countries, others continue to struggle. There has been an upsurge of literature… Continue reading COVID-19 update: April 11, 2020
It has been a long, hard week of complete lockdown in India. We have not seen a significant impact yet, it is probably too early. However, there is a disturbing trend in the number of new COVID-19 cases, although, thankfully, the mortality has remained low. Many other countries are struggling, with a seemingly uncontrollable increase… Continue reading COVID-19 update: April 3, 2020
We are entering an extremely crucial phase of the COVID-19 pandemic, with many countries, including India, closing their borders and enforcing complete lockdown. Clinicians are passing through a learning curve with increasing real-world experience. New information regarding the causative virus, transmission control, and innovative modalities of treatment are being addressed. This review attempts to summarize… Continue reading COVID-19 update: 26th March, 2020
COVID-19 disease has spread far and wide across the globe. At the time of writing, more than 225,000 patients have been affected, leading to more than 9,300 deaths (1). The number of seriously ill patients who require intensive care is likely to increase, requiring several-fold increase in the requirement for caregivers and equipment. The clinical management… Continue reading Management of the critically ill patient with COVID-19 disease
Beginning from December 8, 2019, several cases of pneumonia of unknown origin were reported from Wuhan, the capital of the Chinese province of Hubei. The initial cluster of cases was traced to the Huanan live animal and seafood market. The causative pathogen has hence been identified as an enveloped RNA beta coronavirus with genealogical similarity… Continue reading Coronavirus disease 2019 (COVID-19) update for critical care physicians
Our planet was born approximately 4.8 billion years ago. A billion years later, the oxygen levels began to rise on the earth’s atmosphere. With the rise in oxygen levels, the first signs of life also appeared on the face of the earth. However, it took several billion years before Joseph Priestly (1774) identified oxygen as… Continue reading Oxygen: the elixir of life or a double-edged sword?
The acute respiratory distress syndrome (ARDS) constitutes 23.4% of mechanically ventilated patients (1). Prevention of ventilator-induced lung injury has typically revolved around the use of tidal volumes of 5–8 ml/kg of predicted body weight and limitation of plateau pressures to 30 cm H2O. However, the lung available for ventilation is significantly reduced and highly variable in… Continue reading Lung protective ventilation: targeting tidal volume and plateau pressure vs. driving pressure
Thrombolytic agents lead to the activation of plasminogen to plasmin, resulting in accelerated clot lysis. They have been used in a variety of thrombotic disorders, including acute pulmonary embolism (PE). Thrombolytic therapy in acute PE has been clearly established to improve arterial oxygenation, reduce pulmonary artery pressure, and results in resolution of filling defects on… Continue reading Thrombolysis for acute pulmonary embolism: one size may not fit all!
The spectrum of clinical disorders arising from raised intra-abdominal pressure (IAP) was recognized from the 19thcentury onwards. Abdominal compartment syndrome (ACS) was first described three decades ago among four patients who underwent surgery for ruptured abdominal aortic aneurysm. ACS manifested within the first 24 hours postoperatively with massive abdominal distension and was characterized by rising ventilation… Continue reading When rising intra-abdominal pressure turns silent killer: the abdominal compartment syndrome
Why look for alternatives for the circulatory support of septic patients? Vasopressor therapy in patients with septic shock has centered around the use of noradrenaline titrated to a target mean arterial pressure. The surviving sepsis guidelines recommend noradrenaline as the first-line vasopressor in sepsis.1 Noradrenaline increases venous return and the left ventricular end-diastolic volume by… Continue reading Circulatory support in septic shock: looking beyond catecholamines
Inappropriately prolonged use of antibiotics has several deleterious effects in critically ill patients. Injudicious administration of broad-spectrum antibiotics for an extended period may lead to new-onset infections with resistant organisms due to selective pressure. Besides adding to the cost of care, drug-related adverse effects resulting from prolonged use may also impact clinical outcomes. Let us… Continue reading Knowing when to stop: shorter duration of antibiotic therapy in the critically ill
What is augmented renal clearance? Augmented renal clearance (ARC) is the phenomenon of enhanced renal function in critically ill patients. ARC is characterized by a higher than predicted increase in the renal elimination of solutes. It occurs due to an increase in glomerular filtration and altered renal tubular function, usually manifest as an increase in… Continue reading Augmented renal clearance: when supranormal renal function may cause harm
Introduction Acute pancreatitis runs a relatively mild course in most patients and responds rapidly to supportive therapy, including adequate pain relief, intravenous fluids, and oral intake when feasible. However, the severe form of the disease is characterized by organ failures and leads to a protracted and often complicated clinical course. Nutritional support is crucial and can… Continue reading What may be the ideal nutritional strategy in acute pancreatitis?
Introduction Acute pancreatitis results from an intense inflammatory reaction resulting most commonly from excessive alcoholism or the presence of gall stones. It runs a relatively mild course in most patients and responds rapidly to supportive therapy including adequate pain relief, intravenous fluids, and oral intake when feasible. However, the severe form of the disease occurs… Continue reading Contentious topics in the management of severe acute pancreatitis
More than half a century ago, Kantrowitz et al. first described the use of an “intra-aortic cardiac assistance system” using a balloon-tipped catheter inserted into the descending thoracic aorta.1 They described two patients who developed cardiogenic shock after acute myocardial infarction. The blood pressure remained low, followed by anuria, in spite of high-dose vasopressor therapy.… Continue reading Intra-aortic balloon counterpulsation in critically ill patients
The rationale for the administration of corticosteroids in septic shock The use of corticosteroids as adjunctive therapy in septic shock has captivated intensive care physicians for over five decades. Many of the early studies used industrial doses of synthetic glucocorticoids, and predictably, led to poor clinical outcomes. The concept of corticosteroid insufficiency related to critical… Continue reading Corticosteroids in septic shock: to do or not to do, that is the question
Administration of fluid boluses is considered to be one of the cornerstones of sepsis resuscitation. The surviving sepsis guidelines continue to ardently recommend a fluid bolus of 30 ml/kg within 3 h of presentation to hospital in patients who are hypotensive and considered to have sepsis.1 Let us consider the physiological rationale behind fluid administration… Continue reading The challenge of fluid therapy in sepsis: when less is more
The physiologic rationale ARDS is a heterogeneous disease process, characterized by a mix of relatively normal, collapsed, fluid-filled, and consolidated alveoli. The functional lung tissue is relatively small, and has been described as the “baby lung” (Fig 1). Cyclical opening and closure of collapsed alveoli leads to shear stress at alveolar interphases and leads to… Continue reading The ART of lung recruitment maneuvers
Control of blood glucose levels among critically ill patients continues to evoke intense attention. Van den Berghe et al., in a landmark study, demonstrated that maintaining blood glucose levels within a narrow range, between 80–110 mg/dl may improve clinical outcomes, including ICU and hospital mortality among patients admitted to a surgical ICU.1 In a similar… Continue reading Blood glucose control in the critically ill: hitting the sweet spot
Following the discovery of penicillin in 1928, and its widespread use in clinical practice from the 1940s, several new antibiotic classes were introduced. Vancomycin was introduced in 1958, followed by the cephalosporins, beta-lactamase inhibitors, and quinolones. However, since the introduction of carbapenems in the 1980s, no new class of antibiotic has been added to our… Continue reading Multidrug-resistant gram-negative bacteria: new therapeutic options