effects of hydrocortisone on development of shock among patients with severe sepsis the HYPRESS Randomized Clinical Trial American Medical Association caring for the critically ill patients Surviving sepsis campaign, to determine weather hydrocortisone therapy in patients with severe sepsis prevents the development of septic shock
Assessment of haemodynamics a critically ill patient and its management has always been a matter if debate. Over time a lot of studies and therapeutic interventions have been carried out. This presentation is a review of such interventions and their impact on the outcome.
Assessment of haemodynamics a critically ill patient and its management has always been a matter if debate. Over time a lot of studies and therapeutic interventions have been carried out. This presentation is a review of such interventions and their impact on the outcome.
The New 2018 SCCM PADIS Guidelines: Quick Hits of Recommendations for Sedatio...Intensive Care Society
Dr. Needham is Professor of Pulmonary and Critical Care Medicine, and of Physical Medicine and Rehabilitation at the Johns Hopkins University in Baltimore, USA. He is Director of the “Outcomes After Critical Illness and Surgery” (OACIS) Research Group and core faculty with the Armstrong Institute for Patient Safety and Quality, both at Johns Hopkins. From a clinical perspective, he is an attending physician in the medical intensive care unit at Johns Hopkins Hospital and Medical Director of the Johns Hopkins Critical Care Physical Medicine and Rehabilitation program.
Dr. Needham received his MD degree from McMaster University in Hamilton, Canada, and completed both his residency in internal medicine and his fellowship in critical care medicine at the University of Toronto. He obtained his PhD in Clinical Investigation from the Bloomberg School of Public Health at Johns Hopkins University. Notably, prior to his medical training, he completed Bachelor and Master degrees in Accounting and practiced in a large international accounting firm, with a focus in the health care field.
Dr. Needham is Principal Investigator on a number of NIH research grants and has authored more than 250 publications. His research interests include evaluating and improving ICU patients’ long-term physical, cognitive and mental health outcomes, including research in the areas of sedation, delirium, early physical rehabilitation, and knowledge translation and quality improvement.
Point of critical care Ultrasound play a pivotal role in management of critically ill patients admitted in ICU . Its usage in this regard is ever growing . Here we discus about pearls and pitfalls of POCUS in Intensive care medicine.
The two major causes of acute right ventricular (RV) failure in ICU patients are acute cor pulmonale (ACP) during acute respiratory distress syndrome (ARDS) and ACP during acute massive pulmonary embolism (PE).
The increase in pulmonary vascular resistance (PVR) in ARDS can be secondary either to « structural » mechanisms related to lung injury per se and to « functional » mechanisms related to the effects of mechanical ventilation with positive end expiratory pressure (PEEP). The latter mechanism is enhanced when PEEP overdistends more than it recruits lung volume and when tidal volume (VT) is high. The recommended protective ventilation with low VT and PEEP adjusted to driving pressure can also reduce the RV afterload. A reduced central blood volume can also play a role in the increase in PVR (extension of the West’s zone 2). In this case, volume administration can reduce the PVR and improve the RV function. Finally, prone positioning also exerts a beneficial effect on RV afterload through a decrease in PVR (lung recruitment, decrease in hypoxic vasoconstriction, increase in central blood volume with decrease in the extent of zone 2).
In acute PE, RV dysfunction is associated with poor outcome. Thrombolytic treatment, which is indicated in cases of severe PE with shock, prevents hemodynamic decompensation in patients with intermediate risk PE, but also results in increased risk of severe hemorrhage and stroke. In the case of PE with low cardiac output and no RV dilatation, fluid administration can be indicated to improve cardiac output. In cases of systemic arterial hypotension, vasopressors such as norepinephrine can be indicated to restore adequate RV perfusion pressure. Indication of inotropic agents such as dobutamine, which improves the RV-pressure artery coupling should be evaluated individually. Surgical pulmonary embolectomy can be indicated when the thrombolytic therapy is contra-indicated in acute PE with shock.
Pesit trial New England Journal of MedicineDr fakhir Raza
first episode of syncope, should we do workup for Pulmonary embolism well simplified criteria D dimer level CT angiogram ventilation perfusion scanning
Intensivist Jeremy Cohen drills down on the thinking and value of using steroids in sepsis and the current evidence base. He also discusses a large international trial in progress to find some new answers to all the uncertainty. The Audio can be found on Intensive Care Network and iTunes.
The New 2018 SCCM PADIS Guidelines: Quick Hits of Recommendations for Sedatio...Intensive Care Society
Dr. Needham is Professor of Pulmonary and Critical Care Medicine, and of Physical Medicine and Rehabilitation at the Johns Hopkins University in Baltimore, USA. He is Director of the “Outcomes After Critical Illness and Surgery” (OACIS) Research Group and core faculty with the Armstrong Institute for Patient Safety and Quality, both at Johns Hopkins. From a clinical perspective, he is an attending physician in the medical intensive care unit at Johns Hopkins Hospital and Medical Director of the Johns Hopkins Critical Care Physical Medicine and Rehabilitation program.
Dr. Needham received his MD degree from McMaster University in Hamilton, Canada, and completed both his residency in internal medicine and his fellowship in critical care medicine at the University of Toronto. He obtained his PhD in Clinical Investigation from the Bloomberg School of Public Health at Johns Hopkins University. Notably, prior to his medical training, he completed Bachelor and Master degrees in Accounting and practiced in a large international accounting firm, with a focus in the health care field.
Dr. Needham is Principal Investigator on a number of NIH research grants and has authored more than 250 publications. His research interests include evaluating and improving ICU patients’ long-term physical, cognitive and mental health outcomes, including research in the areas of sedation, delirium, early physical rehabilitation, and knowledge translation and quality improvement.
Point of critical care Ultrasound play a pivotal role in management of critically ill patients admitted in ICU . Its usage in this regard is ever growing . Here we discus about pearls and pitfalls of POCUS in Intensive care medicine.
The two major causes of acute right ventricular (RV) failure in ICU patients are acute cor pulmonale (ACP) during acute respiratory distress syndrome (ARDS) and ACP during acute massive pulmonary embolism (PE).
The increase in pulmonary vascular resistance (PVR) in ARDS can be secondary either to « structural » mechanisms related to lung injury per se and to « functional » mechanisms related to the effects of mechanical ventilation with positive end expiratory pressure (PEEP). The latter mechanism is enhanced when PEEP overdistends more than it recruits lung volume and when tidal volume (VT) is high. The recommended protective ventilation with low VT and PEEP adjusted to driving pressure can also reduce the RV afterload. A reduced central blood volume can also play a role in the increase in PVR (extension of the West’s zone 2). In this case, volume administration can reduce the PVR and improve the RV function. Finally, prone positioning also exerts a beneficial effect on RV afterload through a decrease in PVR (lung recruitment, decrease in hypoxic vasoconstriction, increase in central blood volume with decrease in the extent of zone 2).
In acute PE, RV dysfunction is associated with poor outcome. Thrombolytic treatment, which is indicated in cases of severe PE with shock, prevents hemodynamic decompensation in patients with intermediate risk PE, but also results in increased risk of severe hemorrhage and stroke. In the case of PE with low cardiac output and no RV dilatation, fluid administration can be indicated to improve cardiac output. In cases of systemic arterial hypotension, vasopressors such as norepinephrine can be indicated to restore adequate RV perfusion pressure. Indication of inotropic agents such as dobutamine, which improves the RV-pressure artery coupling should be evaluated individually. Surgical pulmonary embolectomy can be indicated when the thrombolytic therapy is contra-indicated in acute PE with shock.
Pesit trial New England Journal of MedicineDr fakhir Raza
first episode of syncope, should we do workup for Pulmonary embolism well simplified criteria D dimer level CT angiogram ventilation perfusion scanning
Intensivist Jeremy Cohen drills down on the thinking and value of using steroids in sepsis and the current evidence base. He also discusses a large international trial in progress to find some new answers to all the uncertainty. The Audio can be found on Intensive Care Network and iTunes.
Acute coronary syndrome for critical care examDr fakhir Raza
This presentation is made to help students prepare for EDIC exam. this is board review for any exam for critical care examining acute MI, myocardial infarction, acute coronary syndrome.
Most about status asthmaticus, you will find from etiology to treatment and ventilator management. This presentation is made with thanks to medscape and other resources.
Strict Glycemic Control in Critically ill patients: The Demise of another ver...Prof. Mridul Panditrao
Prof. Mridul M. Panditrao tries to explain the pros and cons about the good strategy, whcih became controversial and almost obsolete. He also tries to tract the whole aspect of the phenomenon and reviews/ RCTs/
Strict (Tight) Glycemic control (SGC/TGC), as it is called, was and still is a good strategy. It can be defined as maintenance of the blood glucose level in the range of 80-110 mg /dl. with help of dose variable and intensive insulin therapy (IIT). Since its introduction, there have been conflicting reports of its efficacy and complications. This resulted in slow but steady neglect of this very good idea leading to its almost complete demise.
An effort has been made in this review, to impartially analyze all the available evidence and try to find the reasons for the negative publicity which led to the neglect or worse still, the wrong use of this protocol. Some suggestions for fair and proper implementation of the strategy are put forward.
etc/
PPT on all important trials of traumatic brain injury. - includes design, setting, statistical analysis,outcome, strength, limitations, conclusion#DECRA#RESCUEicp#BEST TRIP#CRASH1#CRASH3#SAFE TBI#EUROTHERM3939#POLAR TRIAL
Also includes trial related BTF guidelines
PEPTIC (Holden Young - Roseman University College of Pharmacy)HoldenYoung3
PEPTIC (Holden Young - Roseman University College of Pharmacy)
Effect of stress ulcer prophylaxis with proton pump inhibitors vs histamine-2 receptor blockers on in-hospital
mortality among ICU patients receiving invasive mechanical ventilation (PEPTIC).
JAMA . 2020; 323(7):616-626
Trial of decompressive craniectomy for traumatic intracranial hypertension1Dr fakhir Raza
The New England Journal of Medicine, Trial of Decompressive Craniectomy for Traumatic Intracranial Hypertension, Extended Glasgow Outcome Scale (GOS-E), vegetative state, lower severe disability, traumatic brain injury, RESCUEicp,
Similar to Effect of hydrocortisone on development of shock among (20)
How to ventilate COPD and ARDS in Intensive care unit. safe lung ventilation. PEEP, Tidal volume, mode of ventilation. limits of ventilation. ventilator alarms
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
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Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
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Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
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Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...
Effect of hydrocortisone on development of shock among
1. Effect of Hydrocortisone on
Development of Shock
Among Patients With Severe Sepsis
The HYPRESS Randomized Clinical
Trial
Dr Fakhir Raza Haidri
25-Oct-2016
Keh. JAMA 2016. Published online October 3, 2016.doi:10.1001/jama.2016.14799
3. Annane D, Sebille V, Charpentier C, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with
septic shock. JAMA. 2002;288(7):862-871.
4. Conclusion
• In our trial, a 7-day treatment with low doses of hydrocortisone and
fludrocortisone significantly reduced the risk of death in patients with
septic shock and relative adrenal insufficiency without increasing
adverse events.
5.
6. Conclusion (CORTICUS)
• Hydrocortisone did not improve survival or reversal of shock in
patients with septic shock, either overall or in patients who did not
have a response to corticotropin, although hydrocortisone hastened
reversal of shock in patients in whom shock was reversed.
7.
8. Conclusion (CIRCI)
• The task force coined the term critical illness-related corticosteroid
insufficiency to describe the dysfunction of the hypothalamic-
pituitary-adrenal axis that occurs during critical illness
• The role of glucocorticoids in the management of patients with
community-acquired pneumonia, liver failure, pancreatitis, those
undergoing cardiac surgery, and other groups of critically ill patients
requires further investigation.
9.
10. Conclusion
• Lancet: Prednisone treatment for 7 days in patients with community-
acquired pneumonia admitted to hospital shortens time to clinical stability
without an increase in complications. This finding is relevant from a patient
perspective and an important determinant of hospital costs and efficiency.
• JAMA: Among patients with severe community-acquired pneumonia and
high initial inflammatory response, the acute use of methylprednisolone
compared with placebo decreased treatment failure.
• Ann intern med: For hospitalized adults with CAP, systemic corticosteroid
therapy may reduce mortality by approximately 3%, need for mechanical
ventilation by approximately 5%, and hospital stay by approximately 1 day
12. Clinical Question
• In patients with severe sepsis does hydrocortisone compared to
placebo prevent the development of septic shock?
13. Method: Design
• Randomised, double-blind, placebo-controlled, multicentre trial
• Internet-based randomisation stratified by participating centre and
sex
• All patients, study personnel, staff were blinded for the entire study
• Intention to treat (and per protocol) analysis
• Assuming 40% of the patients in the placebo group would develop
septic shock, to detect a 15% difference with the intervention arm
(p<0.05, power of 80%), 169 patients per arm were required.
Accounting for a drop out of ~10%, 190 patients per arm (380 total)
were included.
19. Population
• Inclusion:
• Evidence of infection (1 of: micro-organism identified in normally sterile body
fluid, identified focus of infection, granulocytes in sterile body fluid, clinically
suspected infection without microbiological evidence)
• Evidence of SIRS (2 of: fever >38°C or hypothermia <36°C, tachycardia
>90bpm, tachypnea >20/min or CO2<33mmHg or mechanically ventilated,
leukocytosis >12000/ul or leucopenia <4000/ul or >10% immature forms)
• Evidence of Organ Dysfunction for not longer than 48 hours (1 of:
encephalopathy, AKI, coagulopathy, pulmonary dysfunction, microcirculatory
dysfunction)
• Informed consent possible from patient or NextOfKin
20. Population
• Exclusion:
• Patients with septic shock, ie patients who are hypotensive despite adequate fluid
resuscitation (MAP<65Hg, SBP<90mmHg) or those needing vasopressors for more
than 4 hours. Transient use of vasopressors ok whilst fluid resuscitation occurs.
• Patients with hypersensitivity to the hydrocortisone or placebo (mannitol)
• Patients regularly on glucocorticoids
• Patients with a condition indicating glucocorticoid therapy
• DNR or moribund patients
• <18 years
• Recent trial participation (30 days)
• Pregnant/Breast-feeding
• Related to study personnel
21. Population
• Patients were NOT EXCLUDED for using etomidate or a short course of
glucocorticoids within 72 hours before enrollment OR using topical or
inhaled glucocorticoids
• 9953 patients with severe sepsis or septic shock were screened and
380 randomized to receive hydrocortisone n=190 or placebo n=190
22. Intervention
• Bolus of hydrocortisone iv 50mg followed by a 24 hour continuous
infusion of 200mg for 5 days, 100mg for Day 6 & 7, 50mg on Day 8 &
9 and 25mg on Day 10 & 11
• The continuous infusion was preferred to prevent unwanted undulation in
blood glucose concentrations
23. Control
• The placebo was lyophilized mannitol which was indistinguishable
from the hydrocortisone (133mg mannitol – a tiny dose compared
with therapeutic mannitol for raised ICP = 1g/kg)
24. End point
• Primary End point: development of septic shock within 14 days, or
discharge from ICU
25.
26. Outcome
• Primary outcome: the occurrence of septic shock within 14 days,
which was assessed daily until day 14 or discharge from ICU
• The intention to treat analysis excluded 27 patients – consent issues, septic
shock at inclusion, or did not receive study medication
• In the ITT population: shock occurred in 36/170 (21.2%) patients in the
hydrocortisone group vs 39/170 (22.9%) patients in the placebo group
(p=0.70, Difference= -1.8% 95% CI -10.7% to 7.2%)
• In the per-protocol analysis there was no difference in development of septic
shock
• Subgroup analysis: medical vs surgical patients, pneumonia, those receiving
study medication for> 48hrs did not reveal any benefit for shock prevention
27. Outcome
• Secondary outcome: No differences between groups:
• Time until development of septic shock or death
• Mortality in ICU and hospital
• Vital status at Day 28, 90 & 180
• Duration of ICU and hospital stay
• SOFA score
• Duration of mechanical ventilation
• Renal replacement therapy
28. Outcome
• In 206 patients, baseline cortisol concentration was checked and the level
rechecked following administration of 250ug corticotropin. The primary and
secondary outcomes in this subgroup were evaluated – 33.5% of these
patients had CIRCI (Critical Illness Related Corticosteroid Insufficiency). No
difference in primary or secondary endpoints between patients with or
without CIRCI
29. Outcome
• Adverse events assessed included muscle strength scores, secondary
infection, hyperglycaemia, gastrointestinal bleeding, delirium and weaning
failure. There were more episodes of hyperglycaemia in the hydrocortisone
group but the total amount of insulin delivered was not significantly different.
Delirium was less common in the hydrocortisone group (placebo group 24.5%
vs hydrocortisone group 11.2%, p=0.01). The other adverse events did not
differ between groups.
30. Discussion
Patient Population or Problem:
Intervention (or Exposure): Which medical event or therapy do you
need to study the effect of?
Comparison (if known): With what will you compare the
intervention's results?
Outcomes: What are the relevant effects (outcomes) you'll be
monitoring?
31. Strengths
• An important question: the use of steroids in sepsis and septic shock
is one of the longest running debates in critical care. This trial
uniquely examines the use of steroids to prevent shock in patients
with established sepsis.
• Allocation concealment
• Blinding
• Intention to treat analysis
• <5% lost to follow-up
32. Weaknesses
• Patients who developed septic shock early may have been missed
because informed consent was necessary before randomisation
• The mortality rate in this trial was relatively low (8.5% at Day 28) so
this was a relatively well cohort compared to other sepsis trials
(reflecting the haemodynamic stability of the patients at the time of
randomization)
• Not all patients had baseline adrenal function assessed. Only certain
sites did this test and it needed to be done before randomization
occurred.
33. Weaknesses
• Etomidate was used in 6.3% (placebo group) and 6.8%
(hydrocortisone group) of patients pre-randomization. Etomidate
selectively inhibits adrenal corticosteroid synthesis which may impact
the overall result
• Patients in the placebo arm were more likely to have received
glucocorticoids pre-randomization and at higher doses (3.4% vs 1.7%,
600mg vs 200mg), but the number of patients involved was small.
34. Conclusions
• Among adults with severe sepsis not in septic shock, the use of
hydrocortisone compared with placebo did not reduce the risk of
septic shock within 14 days.
• These findings do not support the use of hydrocortisone in these
patients.