Good morning.
Several interesting studies have been presented at the ESICM meeting in Paris. Some of these have simultaneously been published online.
One such study, attempted to evaluate the risk benefit aspects of stress ulcer prophylaxis (SUP) among critically ill patients. Although SUP is extensively prescribed and is considered as a quality marker for ICU care, concerns have been raised of late about the increased incidence of nosocomial pneumonia and diarrhea attributable to SUP. This study aimed to answer some of those concerns
Krag et al: Pantoprazole in Patients at Risk for Gastrointestinal Bleeding in the ICU. NEJM Oct 24 2018
This was a multi center, blinded RCT carried out in Europe. The authors hypothesized that SUP with Pantoprazole would decrease the incidence of Gastro Intestinal Bleeding while increasing the incidence of nosocomial infections and Myocardial Ischemia.
The patients included in this study had to have atleast one risk factor for clinically important GI bleeding among shock, oral anticoagulant usage, renal replacement therapy, need for mechanical ventilation > 24 hours, history of liver disease or ongoing coagulopathy. Pantoprazole was used as SUP as an intravenous injection of 40 mg diluted in 10ml of 0.9% saline. A matching placebo was used.
The primary end point of interest was 90 day mortality. Secondary end points included clinically important gastrointestinal bleeding, new-onset pneumonia, C. difficile infection, or acute myocardial ischemia. Need for RRT and Mechanical ventilation were also included as end points.
This study was carried out between January 2016 and October 2017, enrolling 3298 patients ( 1645 - pantoprazole 1653 placebo). More than 3/4ths of the patients needed mechanical ventilation and more than 2/3rds required vasopressor support. Median SOFA scores of the cohort was 9. More than half the patients received enteral nutrition on the first day of the trial. Average LOS was 6 days and duration of therapy was 4 days.
At the end of 90 days, approximately 30% of patients in both arms had died. There was no difference between the Pantoprazole and the placebo groups. Clinically important events like gi bleed, infection or myocardial ischemia happened in 21-22% of the patients in both the groups. Specifically, GI bleed occurred in 2.8% of patients receiving pantoprazole and 4.2% patients receiving placebo. This difference was statistically insignificant. There were no serious adverse incidents in either group.
The authors concluded that " 90-day mortality, percentages of days alive without the use of life support, and numbers of patients with clinically important events, infectious adverse events, or serious adverse reactions were similar between those treated with pantoprazole and those who received placebo". At the same time incidence of myocardial ischemia and nosocomial infections were not higher in the pantoprazole group.
My opinion: A serious rethinking has to happen regarding the " routine" use of SUP with Pantoprazole. Although the concerns of harm have been partially allayed, the basis for blanket use for all comers is also under question. If enteral feed can be started on the first day, addition of pantoprazole may not confer any additional benefit.
Wednesday, October 24, 2018
Sunday, October 14, 2018
Early versus Late RRT - Should the paradigm change?
Good morning
This week we discuss the results of the IDEAL - ICU ( The Initiation of Dialysis Early Versus Delayed in the Intensive Care Unit ) study which appears to challenge the benefits of early RRT in the ICU.
Barbar et al Timing of Renal-Replacement Therapy in Patients with Acute Kidney Injury and Sepsis.
N Engl J Med 2018; 379: 1431-42
Acute Kidney Injury is very frequent amongst critically ill septic patients. Attributable mortality is also high. The popular belief is that early aggressive RRT is beneficial in terms of ICU survival and long term recovery of renal function.
The IDEAL ICU multicenter study attempted to evaluate whether initiating RRT as soon as a diagnosis of "Failure" as per RIFLE criteria is made, confers survival advantage to the critically ill patient.
They identified patients who satisfied the criteria to define Failure as per the RIFLE criteria. They then randomized this cohort into those who received RRT as soon as failure was diagnosed and into those in whom RRT was initiated only when metabolic problems or hyperkalemia or fluid overload mandated such therapy.
Originally this study was designed to recruit 800+ patients to show a 10% difference in outcomes with 80% power. The primary end point was 90 day mortality. Secondary outcomes were death at 28 days and at 180 days, RRT free days, ventilator and vasopressor free days at 28 days, ICU and hospital LOS, adverse events during the entire ICU stay, fluid balance in the first 7 days after enrollment; the need for emergency renal-replacement therapy in the delayed strategy group; death of patients in the delayed strategy group in whom at least one criterion for emergency renal-replacement therapy was met; and dependence on renal-replacement therapy at hospital discharge.
The study was stopped midway due to apparent futility of the early RRT strategy. Fluid balance also did not show any beneficial pattern with early RRT. The incidence of metabolic complications was higher in the delayed RRT group. Emergency RRT was needed in 17% of patients in the delayed group ( 41 patients). Twenty eight of the 41 died. The dependence on the RRT at hospital discharge was also not significantly different between the two groups.
The authors concluded that " Among patients with septic shock who had severe acute kidney injury, there was no significant difference in overall mortality at 90 days between patients who were assigned to an early strategy for the initiation of renal-replacement therapy and those who were assigned to a delayed strategy."
My view:
1. We need to think twice before initiating RRT just on the basis of creatinine.
2. Failure may not be the ideal comparator. Injury stage may need to be focused on
3. In the delayed strategy emergency need for RRT could be associated with higher mortality
This week we discuss the results of the IDEAL - ICU ( The Initiation of Dialysis Early Versus Delayed in the Intensive Care Unit ) study which appears to challenge the benefits of early RRT in the ICU.
Barbar et al Timing of Renal-Replacement Therapy in Patients with Acute Kidney Injury and Sepsis.
N Engl J Med 2018; 379: 1431-42
Acute Kidney Injury is very frequent amongst critically ill septic patients. Attributable mortality is also high. The popular belief is that early aggressive RRT is beneficial in terms of ICU survival and long term recovery of renal function.
The IDEAL ICU multicenter study attempted to evaluate whether initiating RRT as soon as a diagnosis of "Failure" as per RIFLE criteria is made, confers survival advantage to the critically ill patient.
They identified patients who satisfied the criteria to define Failure as per the RIFLE criteria. They then randomized this cohort into those who received RRT as soon as failure was diagnosed and into those in whom RRT was initiated only when metabolic problems or hyperkalemia or fluid overload mandated such therapy.
Originally this study was designed to recruit 800+ patients to show a 10% difference in outcomes with 80% power. The primary end point was 90 day mortality. Secondary outcomes were death at 28 days and at 180 days, RRT free days, ventilator and vasopressor free days at 28 days, ICU and hospital LOS, adverse events during the entire ICU stay, fluid balance in the first 7 days after enrollment; the need for emergency renal-replacement therapy in the delayed strategy group; death of patients in the delayed strategy group in whom at least one criterion for emergency renal-replacement therapy was met; and dependence on renal-replacement therapy at hospital discharge.
The study was stopped midway due to apparent futility of the early RRT strategy. Fluid balance also did not show any beneficial pattern with early RRT. The incidence of metabolic complications was higher in the delayed RRT group. Emergency RRT was needed in 17% of patients in the delayed group ( 41 patients). Twenty eight of the 41 died. The dependence on the RRT at hospital discharge was also not significantly different between the two groups.
The authors concluded that " Among patients with septic shock who had severe acute kidney injury, there was no significant difference in overall mortality at 90 days between patients who were assigned to an early strategy for the initiation of renal-replacement therapy and those who were assigned to a delayed strategy."
My view:
1. We need to think twice before initiating RRT just on the basis of creatinine.
2. Failure may not be the ideal comparator. Injury stage may need to be focused on
3. In the delayed strategy emergency need for RRT could be associated with higher mortality
Tuesday, October 9, 2018
Have we found an answer to DVT prophylaxis in Neurosurgical patients
Deep Vein Thrombosis is a well recognized complication amongst hospitalized patients. Providing prophylaxis against DVT is acknowledged as a high impact intervention. Neurosurgical patients ( cranial and spinal) constitute a special cohort. On the one hand the incidence of DVT amongst this population is as high as 40%. On the other hand, use of chemical prophylaxis is viewed with caution and with the fear of producing a major hemorrhage. Mechanical prophylaxis has been used as an alternative. But the relative risk reduction with mechanical prophylaxis is not very high. Several attempts have been made in the past to review literature related to this aspect. But the results have been ambiguous.
Khan et al have carried out the latest meta analysis to answer the question of safety of chemical prophylaxis in relation to neurosurgical patients.
Chemical venous thromboembolism prophylaxis in neurosurgical patients: an updated systematic review and meta-analysis
Nickalus R Khan et al J Neurosurg 129:906–915, 2018
The authors carried out a search of literature to identify studies which evaluated the efficacy and safety of chemical prophylaxis among patients undergoing cranial and spinal surgery. Studies which didn't have a control or placebo arm were not included. The funnel plot of the overall study list appears symmetrical excluding publication bias. A total of 9 studies withstood the methodological scrutiny and were eligible for the meta analysis.
The chemical prophylaxis used in six of the studies included was enoxaparin.
The total patient base for this study was 1232. Chemical prophylaxis showed a significant benefit in preventing DVT when compared to placebo with an OR of 0.51. The absolute risk reduction was 42%. The number needed to treat (NNT) for prevention of DVT was 11. The heterogeneity I2 statistic was 0%.
The incidence of major Intra Cranial Hemorrhage in the treatment group was 2.7% compared to 1.6% in the control group. The OR was 1.42, 95% CI 0.61–3.30 which was not statistically significant. The Forrest plots of both these data is shown below.
The rates of major extra cranial bleeds and overall minor bleeds were also not significantly different.
This study seems to conclude that there is a significant benefit in using chemical prophylaxis in prevention of DVT amongst neurosurgical patients with no significant increase in the incidence of major intra cranial hemorrhage.
My opinion: DVTpharmaco prophylaxis amongst Neurosurgical patients may now be approached with a little more confidence. However, close monitoring is needed.
Khan et al have carried out the latest meta analysis to answer the question of safety of chemical prophylaxis in relation to neurosurgical patients.
Chemical venous thromboembolism prophylaxis in neurosurgical patients: an updated systematic review and meta-analysis
Nickalus R Khan et al J Neurosurg 129:906–915, 2018
The authors carried out a search of literature to identify studies which evaluated the efficacy and safety of chemical prophylaxis among patients undergoing cranial and spinal surgery. Studies which didn't have a control or placebo arm were not included. The funnel plot of the overall study list appears symmetrical excluding publication bias. A total of 9 studies withstood the methodological scrutiny and were eligible for the meta analysis.
The chemical prophylaxis used in six of the studies included was enoxaparin.
The total patient base for this study was 1232. Chemical prophylaxis showed a significant benefit in preventing DVT when compared to placebo with an OR of 0.51. The absolute risk reduction was 42%. The number needed to treat (NNT) for prevention of DVT was 11. The heterogeneity I2 statistic was 0%.
The incidence of major Intra Cranial Hemorrhage in the treatment group was 2.7% compared to 1.6% in the control group. The OR was 1.42, 95% CI 0.61–3.30 which was not statistically significant. The Forrest plots of both these data is shown below.
The rates of major extra cranial bleeds and overall minor bleeds were also not significantly different.
This study seems to conclude that there is a significant benefit in using chemical prophylaxis in prevention of DVT amongst neurosurgical patients with no significant increase in the incidence of major intra cranial hemorrhage.
My opinion: DVTpharmaco prophylaxis amongst Neurosurgical patients may now be approached with a little more confidence. However, close monitoring is needed.
Monday, October 1, 2018
Can Response to Iron therapy in ICU be predicted
Anemia in the Intensive Care Unit is a common problem. Transfusion triggers are getting lower across specialties as discussed last week. Iron infusion therapy is sometimes used to augment the marrow response to the stress of critical illness. But, the effect of iron therapy on reducing the transfusion requirement has not been reported. Litton et al attempted to evaluate the efficacy of Hepcidin in predicting the response to iron therapy and thereby reduce transfusion requirements. This was a nested cohort as a part of the IRONMAN study.
Hepcidin predicts response to IV iron therapy in patients admitted to the intensive care unit: a nested cohort study.
Litton et al. Journal of Intensive Care (2018) 6:60
This was a prospective observational study across four tertiary care Australian ICUs which participated in the IRONMAN study.
The response to Iron therapy among critically ill patients is variable. Hepcidin is an integral part of the iron metabolism and serum levels fall in iron deficiency states.
The primary aim of this study was to determine whether low serum hepcidin concentration could identify a subset of critically ill patients with anaemia in whom IV iron therapy was effective in reducing RBC transfusion requirement.
Septic patients and those with well established Iron deficiency were excluded.
The treatment arm received 500 mg IV ferric carboxy maltose. Hepcidin 25 levels were measured prior to administration of parenteral Iron
A total of 133 patients were included in this study
Majority of the patients were post operative patients predominantly from trauma and cardiothoracic ORs. APACHE II score was 12 and mean SOFA score was 6. Eighty eight patients fell in the lower two tertiles of hepcidin concentration. Half of them received parenteral iron and the other half received placebo. Patients who had lower hepcidin concentration responded to Iron and required lesser packed cell transfusions. Patients who had Hepcidin concentration in the highest tertile did not show any decreased requirement for blood transfusion despite iron therapy. Hepcidin levels did not correlate with standard determinants of iron deficiency like transferrin saturation index.
The authors surmised that serum hepcidin concentration identified a subset of anaemic, critically ill patients in whom IV iron therapy was effective in reducing RBC transfusion requirement.
What I understood?
Predicting response to iron therapy is always difficult and unpredictable. Using the Hepcidin level, if response to therapy can be predicted, lot of blood transfusions can be safely avoided
Where this study fails?
No septic patients included
No correlation with perfusion markers.
Hepcidin predicts response to IV iron therapy in patients admitted to the intensive care unit: a nested cohort study.
Litton et al. Journal of Intensive Care (2018) 6:60
This was a prospective observational study across four tertiary care Australian ICUs which participated in the IRONMAN study.
The response to Iron therapy among critically ill patients is variable. Hepcidin is an integral part of the iron metabolism and serum levels fall in iron deficiency states.
The primary aim of this study was to determine whether low serum hepcidin concentration could identify a subset of critically ill patients with anaemia in whom IV iron therapy was effective in reducing RBC transfusion requirement.
Septic patients and those with well established Iron deficiency were excluded.
The treatment arm received 500 mg IV ferric carboxy maltose. Hepcidin 25 levels were measured prior to administration of parenteral Iron
A total of 133 patients were included in this study
Majority of the patients were post operative patients predominantly from trauma and cardiothoracic ORs. APACHE II score was 12 and mean SOFA score was 6. Eighty eight patients fell in the lower two tertiles of hepcidin concentration. Half of them received parenteral iron and the other half received placebo. Patients who had lower hepcidin concentration responded to Iron and required lesser packed cell transfusions. Patients who had Hepcidin concentration in the highest tertile did not show any decreased requirement for blood transfusion despite iron therapy. Hepcidin levels did not correlate with standard determinants of iron deficiency like transferrin saturation index.
The authors surmised that serum hepcidin concentration identified a subset of anaemic, critically ill patients in whom IV iron therapy was effective in reducing RBC transfusion requirement.
What I understood?
Predicting response to iron therapy is always difficult and unpredictable. Using the Hepcidin level, if response to therapy can be predicted, lot of blood transfusions can be safely avoided
Where this study fails?
No septic patients included
No correlation with perfusion markers.
Sunday, September 23, 2018
Is the last bastion of blood transfusion falling?
Good Morning
Today, we report the findings of a meta analysis evaluating the effect of blood transfusion on long term and short term outcomes amongst patients with STEMI.
Red blood cell transfusion in patients with ST-elevation myocardial infarction—a meta-analysis of more than 21,000 patients.
Mincu R I et al
Neth Heart J (2018) 26:454–460
The indications for transfusions in critically ill patients are narrowing down. More and more evidence seems to be pointing towards harm with liberal transfusion triggers. One of the subsets of patients where liberalism has been accepted is STEMI. It is hypothesized that lower Hb levels potentiate the genesis of ischemia and may be detrimental to the outcomes among patients with STEMI. Well designed RCTs evaluating transfusion triggers in STEMI are also understandably lacking.
Mincu et al carried out a meta analysis "to determine the impact of RBT on short-term and long term outcomes in patients with STEMI, in order to address the gaps in knowledge in the management of these patients.
In the absence of RCTs, 5 well designed high quality cohort studies were chosen for the meta analysis. More than 21000 patients were identified. 984 patients received transfusion. Patients who received transfusion had higher prevalence of DM and HTN. Previous MI, CABG and stroke rates were comparable between the two cohorts. Premorbid conditions seem to be higher in the cohort which received transfusions. The mean minimum Hb in the transfusion group was 8.5gm/dl. Patients who received transfusion had a higher in hospital mortality. The risk of long term mortality was also higher amongst patients with STEMI who received blood transfusions. More importantly, reinfarction rates were higher in those who received blood transfusions. More patients in the STEMI with transfusions progressed to heart failure.
What I understood:
1. Comorbidities associated with lower Hb are often the triggers for transfusion.
2. Patients with STEMI with lower Hb levels do worse that those with higher Hb
3. Correcting the Hb with Blood transfusions does not confer any benefit.
Good Morning
Today, we report the findings of a meta analysis evaluating the effect of blood transfusion on long term and short term outcomes amongst patients with STEMI.
Red blood cell transfusion in patients with ST-elevation myocardial infarction—a meta-analysis of more than 21,000 patients.
Mincu R I et al
Neth Heart J (2018) 26:454–460
The indications for transfusions in critically ill patients are narrowing down. More and more evidence seems to be pointing towards harm with liberal transfusion triggers. One of the subsets of patients where liberalism has been accepted is STEMI. It is hypothesized that lower Hb levels potentiate the genesis of ischemia and may be detrimental to the outcomes among patients with STEMI. Well designed RCTs evaluating transfusion triggers in STEMI are also understandably lacking.
Mincu et al carried out a meta analysis "to determine the impact of RBT on short-term and long term outcomes in patients with STEMI, in order to address the gaps in knowledge in the management of these patients.
In the absence of RCTs, 5 well designed high quality cohort studies were chosen for the meta analysis. More than 21000 patients were identified. 984 patients received transfusion. Patients who received transfusion had higher prevalence of DM and HTN. Previous MI, CABG and stroke rates were comparable between the two cohorts. Premorbid conditions seem to be higher in the cohort which received transfusions. The mean minimum Hb in the transfusion group was 8.5gm/dl. Patients who received transfusion had a higher in hospital mortality. The risk of long term mortality was also higher amongst patients with STEMI who received blood transfusions. More importantly, reinfarction rates were higher in those who received blood transfusions. More patients in the STEMI with transfusions progressed to heart failure.
What I understood:
1. Comorbidities associated with lower Hb are often the triggers for transfusion.
2. Patients with STEMI with lower Hb levels do worse that those with higher Hb
3. Correcting the Hb with Blood transfusions does not confer any benefit.
Sunday, September 16, 2018
Some interesting articles
Muñoz. Primary decompressive craniectomy in neurocritical patients. a meta-analysis of randomized controlled trials, cohort and case-control studies. J Emerg Crit Care Med 2018;2:73
Lilly. Comparative Effectiveness of Proton Pump Inhibitors vs Histamine Type 2 Receptor Blockers for Preventing Clinically Important Gastrointestinal Bleeding During Intensive Care. A Population-Based Study. Chest 2018;154(3):557–566
Rahul. Effects of positive end-expiratory pressure strategy in supine and prone position on lung and chest wall mechanics in acute respiratory distress syndrome. Ann Intensive Care 2018;8(1):86Ann Intensive Care 2018;8(1):86
Kaliyaperumal. Pharmacogenomics of drug-induced liver injury (DILI): Molecular biology to clinical applications. J Hepatology 2018;69(4):948-957
Muñoz. Primary decompressive craniectomy in neurocritical patients. a meta-analysis of randomized controlled trials, cohort and case-control studies. J Emerg Crit Care Med 2018;2:73
Lilly. Comparative Effectiveness of Proton Pump Inhibitors vs Histamine Type 2 Receptor Blockers for Preventing Clinically Important Gastrointestinal Bleeding During Intensive Care. A Population-Based Study. Chest 2018;154(3):557–566
Rahul. Effects of positive end-expiratory pressure strategy in supine and prone position on lung and chest wall mechanics in acute respiratory distress syndrome. Ann Intensive Care 2018;8(1):86Ann Intensive Care 2018;8(1):86
Kaliyaperumal. Pharmacogenomics of drug-induced liver injury (DILI): Molecular biology to clinical applications. J Hepatology 2018;69(4):948-957
Good Morning
This weeks review is related to the use of recruitment maneuvers for moderate to severe ARDS guided by echo cardiography.
Moderate and Severe Acute Respiratory Distress Syndrome: Hemodynamic and Cardiac Effects of an Open Lung Strategy With Recruitment Maneuver Analyzed Using Echocardiography.
Mercado et al
Crit Care Med 2018; 46:1608–1616
Moderate to severe ARDS is still a therapeutic challenge. Achieving acceptable goals of oxygenation among these patients is offset quite often by the fear of hemodynamic compromise. Recruitment maneuvers have not found strong evidence based backing. However, there might be yet some subset of patients who need and benefit from recruitment maneuvers. Identifying the optimum PEEP also remains a tricky proposition.
Mercado et al in a prospective observational study attempted to evaluate a decremental PEEP strategy combined with echocardiographic assessment of LV and RV function and strain. Their hypothesis was based on a premise that recruitment maneuvers and high PEEP applied during the expiratory limb of the PV curve is safer for both the lung and the heart.
They identified patients with moderate to severe ARDS as per the Berlin definition. They ensured euvolemia by using the PLR maneuver and correcting it prior to application of the recruitment maneuver. All patients had invasive arterial pressure as well as CVP monitoring. They applied the principle of coronary perfusion pressure as defined by MAP - CVP. RV and LV strain were also measured along with End Diastolic Volumes and TAPSE/MAPSE.
All the study patients were paralysed. Recruitment was started by applying a PEEP of 25 cm H2O with a driving pressure of 15 cm H2O. PEEP was then incrementally increased by 5 cm H2O every 2 minutes with a constant driving pressure until a PEEP of 40 cm H2O was reached. Once this level of PEEP was reached, PEEP was reset to 25-15 and decrement strategy started. Decrement was achieved at 5 cm H20 of PEEP every 4 minutes. Oxygen saturation and compliance were measured to identify the point of termination of decreasing PEEP. A fall in SpO2 by > 2% or compliance by > 2 ml /cm H2O were the triggers to stop PEEP. From this point recruitment as described above was repeated again and PEEP was reduced to a level higher than previous start level.
Hemodynamics were assessed by MAP, CVP, Coronary Perfusion Pressure and Echocardiography both at peak recruitment as well as at optimum PEEP.
The effects of recruitment maneuvers were dramatic. The Systolic pressure fell by 17% , DBP by 14%, MAP by 15 % SV by 19% and CO by 20% between optimum and peak PEEP levels. The CVP rose significantly to cause a fall of Coronary Perfusion Pressure by 37%. These changes were transient and reverted to baseline within a hour of downsizing the PEEP. LV strain and RV strain were also noted.
Non responders were identified by several parameters. Non responders had higher RVEDA/LVEDA ratios. All hemodynamic parameters had far greater decrements in non responders than amongst responders.
What the authors say:
This study demonstrates that in patients with moderate to severe ARDS, a slow stepwise RM is associated with oxygenation improvement and transient and reversible right and left cardiac dysfunction. Furthermore, setting a higher PEEP after this RM dramatically improved both oxygenation and lung function without any deterioration in either LV or RV function.
An open lung strategy achieved by a slow stepwise RM appears to be beneficial for the lung while not resulting in negative effects on the heart.
My views:
1. This study shows the value of hemodynamic monitoring during recruitment.
2. Recruitment maneuvers are not hemodynamically neutral
3. Hemodynamic assessment could identify those who may not benefit from RM
4. This is a small study of 20 patients each. May not find favor as EBM, but has a sound physiological basis
This weeks review is related to the use of recruitment maneuvers for moderate to severe ARDS guided by echo cardiography.
Moderate and Severe Acute Respiratory Distress Syndrome: Hemodynamic and Cardiac Effects of an Open Lung Strategy With Recruitment Maneuver Analyzed Using Echocardiography.
Mercado et al
Crit Care Med 2018; 46:1608–1616
Moderate to severe ARDS is still a therapeutic challenge. Achieving acceptable goals of oxygenation among these patients is offset quite often by the fear of hemodynamic compromise. Recruitment maneuvers have not found strong evidence based backing. However, there might be yet some subset of patients who need and benefit from recruitment maneuvers. Identifying the optimum PEEP also remains a tricky proposition.
Mercado et al in a prospective observational study attempted to evaluate a decremental PEEP strategy combined with echocardiographic assessment of LV and RV function and strain. Their hypothesis was based on a premise that recruitment maneuvers and high PEEP applied during the expiratory limb of the PV curve is safer for both the lung and the heart.
They identified patients with moderate to severe ARDS as per the Berlin definition. They ensured euvolemia by using the PLR maneuver and correcting it prior to application of the recruitment maneuver. All patients had invasive arterial pressure as well as CVP monitoring. They applied the principle of coronary perfusion pressure as defined by MAP - CVP. RV and LV strain were also measured along with End Diastolic Volumes and TAPSE/MAPSE.
All the study patients were paralysed. Recruitment was started by applying a PEEP of 25 cm H2O with a driving pressure of 15 cm H2O. PEEP was then incrementally increased by 5 cm H2O every 2 minutes with a constant driving pressure until a PEEP of 40 cm H2O was reached. Once this level of PEEP was reached, PEEP was reset to 25-15 and decrement strategy started. Decrement was achieved at 5 cm H20 of PEEP every 4 minutes. Oxygen saturation and compliance were measured to identify the point of termination of decreasing PEEP. A fall in SpO2 by > 2% or compliance by > 2 ml /cm H2O were the triggers to stop PEEP. From this point recruitment as described above was repeated again and PEEP was reduced to a level higher than previous start level.
Hemodynamics were assessed by MAP, CVP, Coronary Perfusion Pressure and Echocardiography both at peak recruitment as well as at optimum PEEP.
The effects of recruitment maneuvers were dramatic. The Systolic pressure fell by 17% , DBP by 14%, MAP by 15 % SV by 19% and CO by 20% between optimum and peak PEEP levels. The CVP rose significantly to cause a fall of Coronary Perfusion Pressure by 37%. These changes were transient and reverted to baseline within a hour of downsizing the PEEP. LV strain and RV strain were also noted.
Non responders were identified by several parameters. Non responders had higher RVEDA/LVEDA ratios. All hemodynamic parameters had far greater decrements in non responders than amongst responders.
What the authors say:
This study demonstrates that in patients with moderate to severe ARDS, a slow stepwise RM is associated with oxygenation improvement and transient and reversible right and left cardiac dysfunction. Furthermore, setting a higher PEEP after this RM dramatically improved both oxygenation and lung function without any deterioration in either LV or RV function.
An open lung strategy achieved by a slow stepwise RM appears to be beneficial for the lung while not resulting in negative effects on the heart.
My views:
1. This study shows the value of hemodynamic monitoring during recruitment.
2. Recruitment maneuvers are not hemodynamically neutral
3. Hemodynamic assessment could identify those who may not benefit from RM
4. This is a small study of 20 patients each. May not find favor as EBM, but has a sound physiological basis
Sunday, September 9, 2018
Good Morning
This week we review an interesting article related to the diagnosis of AKI using an easily measured parameter. Identifying AKI at KDIGO > 1 stage is difficult. However, early identification helps to minimize the morbidity associated with Kidney Injury and RRT. Several biomarkers are available and several more are under investigation. Burns et al used K excretion and compared it to creatinine clearance and attempted to correlate this with a diagnosis of AKI.
Urinary potassium excretion and its association with acute kidney injury in the intensive care unit.
Burns et al
Journal of Critical Care 46 (2018) 58–62
This is a prospective cohort study which attempted to measure 2 hr K excretion and correlate it with conventionally measured creatinine clearance. The data obtained was used to predict AKI over the subsequent 7 days in ICU. The basic hypothesis was that K excretion is reduced in AKI and could be used to discriminate those who developed AKI over the next 7 days from those who did not. Urine sample collected between 0400-0600 hrs was analysed for K Na and Creatinine concentrations. Around 60 patients were enrolled in the study. 62% were male. Post operative and trauma patients made up close to 50% of the cohort. A quarter of the cohort needed vasopressors. The mean APACHE II score of the cohort was 15. The total amount of urinary potassium excreted in 2-h was calculated by multiplying the 2-hour urine sample potassium concentration (mmol/l) by the urine volume (litres in the 2 h collection period) to give m mol of potassium excreted in 2 h. All patients were followed up to hospital discharge capturing data on the peak plasma creatinine concentration within 7 days of enrolment and during the whole hospital stay, KDIGO AKI grading after enrolment, RRT, and mortality. In patients who did not receive frusemide the urinary potassium excretion correlated linearly with the simultaneously calculated creatinine clearance. Frusemide seemed to be decrease this correlation. This correlation was found to be better that Na excretion or Renal SOFA for the prediction on AKI.
Based on the AUROC curve of urinary potassium excretion, using a cut-point of urinary potassium excretion ≤3.8mmol in 2 h would have a specificity of 85% and sensitivity of 77% in predicting subsequent AKI (KDIGO stage ≥1) within 7 days of testing. This is different from the relationship between urinary sodium excretion and the calculated Cr Cl or risk of subsequent
AKI.
What it means: This study gives an easily measurable parameter to predict the onset of AKI in a cohort of patients at risk of AKI. However, it remains to be seen whether it can be applied to patients with higher APACHE scores. The effect of augmented renal clearance on this parameter also needs to be evaluated
This week we review an interesting article related to the diagnosis of AKI using an easily measured parameter. Identifying AKI at KDIGO > 1 stage is difficult. However, early identification helps to minimize the morbidity associated with Kidney Injury and RRT. Several biomarkers are available and several more are under investigation. Burns et al used K excretion and compared it to creatinine clearance and attempted to correlate this with a diagnosis of AKI.
Urinary potassium excretion and its association with acute kidney injury in the intensive care unit.
Burns et al
Journal of Critical Care 46 (2018) 58–62
This is a prospective cohort study which attempted to measure 2 hr K excretion and correlate it with conventionally measured creatinine clearance. The data obtained was used to predict AKI over the subsequent 7 days in ICU. The basic hypothesis was that K excretion is reduced in AKI and could be used to discriminate those who developed AKI over the next 7 days from those who did not. Urine sample collected between 0400-0600 hrs was analysed for K Na and Creatinine concentrations. Around 60 patients were enrolled in the study. 62% were male. Post operative and trauma patients made up close to 50% of the cohort. A quarter of the cohort needed vasopressors. The mean APACHE II score of the cohort was 15. The total amount of urinary potassium excreted in 2-h was calculated by multiplying the 2-hour urine sample potassium concentration (mmol/l) by the urine volume (litres in the 2 h collection period) to give m mol of potassium excreted in 2 h. All patients were followed up to hospital discharge capturing data on the peak plasma creatinine concentration within 7 days of enrolment and during the whole hospital stay, KDIGO AKI grading after enrolment, RRT, and mortality. In patients who did not receive frusemide the urinary potassium excretion correlated linearly with the simultaneously calculated creatinine clearance. Frusemide seemed to be decrease this correlation. This correlation was found to be better that Na excretion or Renal SOFA for the prediction on AKI.
Based on the AUROC curve of urinary potassium excretion, using a cut-point of urinary potassium excretion ≤3.8mmol in 2 h would have a specificity of 85% and sensitivity of 77% in predicting subsequent AKI (KDIGO stage ≥1) within 7 days of testing. This is different from the relationship between urinary sodium excretion and the calculated Cr Cl or risk of subsequent
AKI.
What it means: This study gives an easily measurable parameter to predict the onset of AKI in a cohort of patients at risk of AKI. However, it remains to be seen whether it can be applied to patients with higher APACHE scores. The effect of augmented renal clearance on this parameter also needs to be evaluated
Monday, September 3, 2018
Good morning
Today we discuss the findings of the EUROTHERM3235 study.
Therapeutic hypothermia to reduce intracranial pressure after traumatic brain injury: the Eurotherm3235 RCT
Peter JD Andrews et al
HEALTH TECHNOLOGY ASSESSMENT VOLUME 22 ISSUE 45 AUGUST 2018
Therapeutic hypothermia (TH) has been a tool for trying to optimize outcomes in various situations encountered in neuro critical care.
TBI and Post Cardiac Arrest situations are the two most commonly used cohorts for evaluating TH
EUROTHERM3235 was a multi centre study which attempted to evaluate whether TH between 32-35 C improves outcomes and decreases mortality at 6 months following TBI. In addition, the secondary outcomes studied included benefits related to intra cranial pressure and cost effectiveness.
The covariates ( or sub groups) identified at the beginning of randomization included
1. trial centre
2. aged < 45 years or ≥ 45 years
3. post-resuscitation Glasgow Coma Scale (GCS) motor component score of 1 or 2 or 3–6
4. time from injury < 12 hours or ≥ 12 hours
5. pupils – both reacting or one or neither reacting.
Hypothermia was initiated with 20–30 ml/kg of refrigerated 0.9% saline given intravenously and maintained using the cooling technique available at each centre.
The depth of hypothermia (32–35 °C) was guided by intracranial pressure (ICP), with a higher pressure level warranting a cooler target temperature. TH of 32–35 °C was maintained for at least 48 hours and continued for as long as was necessary to reduce and maintain ICP at < 20 mmHg.
Since initiation of hypothermia could not be blinded, the outcome assessment was done by a blinded researcher.
Screening for inclusion was done up to ten days after the injury.
Inclusion criteria were
Primary closed TBI.
Raised ICP of > 20 mmHg for ≥ 5 minutes after first-line treatments with no obvious reversible cause (e.g. patient position, coughing, inadequate sedation).
≤ 10 days from the initial head injury.
Cooling device or technique available for > 48 hours.
Core temperature of ≥ 36 °C (at the time of randomization).
An abnormal CT scan of the brain, defined as one that shows haematoma, contusion, swelling,
herniation or compressed basal cisterns.
Exclusion criteria were
Patient already receiving TH treatment.
Administration of barbiturate infusion prior to randomisation.
Unlikely to survive for the next 24 hours in the opinion of the ICU consultant or consultant
neurosurgeon treating the patient.
Temperature of ≤ 34 °C at hospital admission.
Pregnancy.
Only centres well versed in ICP management and TH protocols were enrolled. More than half of the eligible centres were in the UK.
A total of 387 participants from 64 centres in 18 countries were randomized.
This study was stopped midway as the steering committee felt that there was possibility of harm with the use of TH. Futility was the outcome predicted.
The odds ratio for unfavorable outcome with TH was 1.69.
The results of the primary analysis were unexpected and showed that participants in the hypothermia
group had significantly poorer outcomes at 6 months (p = 0.04) and a higher mortality rate (p = 0.05) than those treated with standard care alone.
ICP control also did not differ in the two groups.
At best, a result of futility would be expected if the trial were to continue.
There were signs of harm with the treatment being evaluated.
These signs included increased mortality in participants assigned to the treatment being evaluated and
fewer participants assigned to the treatment being evaluated achieving ‘good recovery’ on the GOSE at the designated outcome assessment point of 6 months after inclusion.
Summary: TH does not appear to be safe in patients being treated for TBI
My views: This is another good physiological concept which has not yielded clinical results. Probably factors other than ICP (and CPP) determine the outcome after TBI
Today we discuss the findings of the EUROTHERM3235 study.
Therapeutic hypothermia to reduce intracranial pressure after traumatic brain injury: the Eurotherm3235 RCT
Peter JD Andrews et al
HEALTH TECHNOLOGY ASSESSMENT VOLUME 22 ISSUE 45 AUGUST 2018
Therapeutic hypothermia (TH) has been a tool for trying to optimize outcomes in various situations encountered in neuro critical care.
TBI and Post Cardiac Arrest situations are the two most commonly used cohorts for evaluating TH
EUROTHERM3235 was a multi centre study which attempted to evaluate whether TH between 32-35 C improves outcomes and decreases mortality at 6 months following TBI. In addition, the secondary outcomes studied included benefits related to intra cranial pressure and cost effectiveness.
The covariates ( or sub groups) identified at the beginning of randomization included
1. trial centre
2. aged < 45 years or ≥ 45 years
3. post-resuscitation Glasgow Coma Scale (GCS) motor component score of 1 or 2 or 3–6
4. time from injury < 12 hours or ≥ 12 hours
5. pupils – both reacting or one or neither reacting.
Hypothermia was initiated with 20–30 ml/kg of refrigerated 0.9% saline given intravenously and maintained using the cooling technique available at each centre.
The depth of hypothermia (32–35 °C) was guided by intracranial pressure (ICP), with a higher pressure level warranting a cooler target temperature. TH of 32–35 °C was maintained for at least 48 hours and continued for as long as was necessary to reduce and maintain ICP at < 20 mmHg.
Since initiation of hypothermia could not be blinded, the outcome assessment was done by a blinded researcher.
Screening for inclusion was done up to ten days after the injury.
Inclusion criteria were
Primary closed TBI.
Raised ICP of > 20 mmHg for ≥ 5 minutes after first-line treatments with no obvious reversible cause (e.g. patient position, coughing, inadequate sedation).
≤ 10 days from the initial head injury.
Cooling device or technique available for > 48 hours.
Core temperature of ≥ 36 °C (at the time of randomization).
An abnormal CT scan of the brain, defined as one that shows haematoma, contusion, swelling,
herniation or compressed basal cisterns.
Exclusion criteria were
Patient already receiving TH treatment.
Administration of barbiturate infusion prior to randomisation.
Unlikely to survive for the next 24 hours in the opinion of the ICU consultant or consultant
neurosurgeon treating the patient.
Temperature of ≤ 34 °C at hospital admission.
Pregnancy.
Only centres well versed in ICP management and TH protocols were enrolled. More than half of the eligible centres were in the UK.
A total of 387 participants from 64 centres in 18 countries were randomized.
This study was stopped midway as the steering committee felt that there was possibility of harm with the use of TH. Futility was the outcome predicted.
The odds ratio for unfavorable outcome with TH was 1.69.
The results of the primary analysis were unexpected and showed that participants in the hypothermia
group had significantly poorer outcomes at 6 months (p = 0.04) and a higher mortality rate (p = 0.05) than those treated with standard care alone.
ICP control also did not differ in the two groups.
At best, a result of futility would be expected if the trial were to continue.
There were signs of harm with the treatment being evaluated.
These signs included increased mortality in participants assigned to the treatment being evaluated and
fewer participants assigned to the treatment being evaluated achieving ‘good recovery’ on the GOSE at the designated outcome assessment point of 6 months after inclusion.
Summary: TH does not appear to be safe in patients being treated for TBI
My views: This is another good physiological concept which has not yielded clinical results. Probably factors other than ICP (and CPP) determine the outcome after TBI
Monday, August 27, 2018
Hi
Today we review a meta analysis evaluating the different treatment options available for Clostridium difficile infection (CDI). This meta analysis attempts to answer a few questions related to an emerging disease in the sub continent
Comparative efficacy of treatments for Clostridium difficile infection: a systematic review and network meta-analysis.
Beinortas et al
Lancet Infect Dis 2018;18: 1035–44
This meta analysis could identify 24 comparative studies which evaluated two or more treatment options for CDI. A total of 5361 patients receiving 13 different treatment options were evaluated. The primary outcome measure was primary cure of diarrhea. Recurrence of infection was not an end point of interest for the meta analysis. Most of the studies included follow up of 28 days. Severity of the disease was not specified in 9 /24 studies. The most common therapy used was vancomycin followed by metronidazole and fidaxomicin. Most of the drugs were compared against Vancomycin. 17/24 studies included were industry sponsored. Teicoplanin and Fidaxomicin performed better than Vancomycin. Metronidazole performed inferiorly compared to most main line drugs. Tolevamer also did not perform well. Ridinilazole was significantly better than vancomycin in attaining a sustained symptomatic cure in patients with mild to moderate infections with C difficile and who were younger than 65 years. Teicoplanin, Ridinilazole and Fidaxomicin were the top three ranked drugs. However, the no of participants in the studies involving Teicoplanin were small and confidence intervals were wide. Ridinilazole appeared to be the best drug for prevention of recurrence in sub group analysis. The advantage of Teicoplanin seemed to decrease in the analysis when non blinded studies were excluded.
Therefore, fidaxomicin has the strongest evidence for being the most effective treatment
in providing a long-term cure against C difficile. Apart from affordability, there is little evidence to support use of metronidazole as a first-line treatment against infections with C difficile.
Early data for ridinilazole suggest that this treatment could potentially become a new, efficacious
treatment against infections with C difficile.
Drawbacks:
Majority of studies are industry sponsored
No stratification of severe infections
My view: Fidaxomicin seems to be the first choice. Teicoplanin can be used in mild to moderate cases. No overwhelming need to stick to Vancomycin. Metronidazole should be avoided.
Today we review a meta analysis evaluating the different treatment options available for Clostridium difficile infection (CDI). This meta analysis attempts to answer a few questions related to an emerging disease in the sub continent
Comparative efficacy of treatments for Clostridium difficile infection: a systematic review and network meta-analysis.
Beinortas et al
Lancet Infect Dis 2018;18: 1035–44
This meta analysis could identify 24 comparative studies which evaluated two or more treatment options for CDI. A total of 5361 patients receiving 13 different treatment options were evaluated. The primary outcome measure was primary cure of diarrhea. Recurrence of infection was not an end point of interest for the meta analysis. Most of the studies included follow up of 28 days. Severity of the disease was not specified in 9 /24 studies. The most common therapy used was vancomycin followed by metronidazole and fidaxomicin. Most of the drugs were compared against Vancomycin. 17/24 studies included were industry sponsored. Teicoplanin and Fidaxomicin performed better than Vancomycin. Metronidazole performed inferiorly compared to most main line drugs. Tolevamer also did not perform well. Ridinilazole was significantly better than vancomycin in attaining a sustained symptomatic cure in patients with mild to moderate infections with C difficile and who were younger than 65 years. Teicoplanin, Ridinilazole and Fidaxomicin were the top three ranked drugs. However, the no of participants in the studies involving Teicoplanin were small and confidence intervals were wide. Ridinilazole appeared to be the best drug for prevention of recurrence in sub group analysis. The advantage of Teicoplanin seemed to decrease in the analysis when non blinded studies were excluded.
Therefore, fidaxomicin has the strongest evidence for being the most effective treatment
in providing a long-term cure against C difficile. Apart from affordability, there is little evidence to support use of metronidazole as a first-line treatment against infections with C difficile.
Early data for ridinilazole suggest that this treatment could potentially become a new, efficacious
treatment against infections with C difficile.
Drawbacks:
Majority of studies are industry sponsored
No stratification of severe infections
My view: Fidaxomicin seems to be the first choice. Teicoplanin can be used in mild to moderate cases. No overwhelming need to stick to Vancomycin. Metronidazole should be avoided.
Sunday, August 19, 2018
A few interesting studies
1.Thomalla. MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset. N Engl J Med 2018;379:611-622
2. Yu. Clinical outcomes of prolonged infusion (extended infusion or continuous infusion) versus intermittent bolus of meropenem in severe infection: A meta-analysis. PLoS One 2018;13(7):e0201667
3. Lindgren. Endovascular coiling versus neurosurgical clipping for people with aneurysmal subarachnoid haemorrhage. Cochrane Database of Systematic Reviews 2018, Issue 8. Art. No.: CD003085
4. Devlin. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med 2018;46(9):e825-e873
A few good reviews as well
Finfer. Intravenous fluid therapy in critically ill adults. Nature Reviews Nephrology 2018;14:541–557
Bussard. Angiotensin II: a new therapeutic option for vasodilatory shock. Ther Clin Risk Manag 2018;14:1287–1298
Please drop a request for full text if needed in the comment box
1.Thomalla. MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset. N Engl J Med 2018;379:611-622
2. Yu. Clinical outcomes of prolonged infusion (extended infusion or continuous infusion) versus intermittent bolus of meropenem in severe infection: A meta-analysis. PLoS One 2018;13(7):e0201667
3. Lindgren. Endovascular coiling versus neurosurgical clipping for people with aneurysmal subarachnoid haemorrhage. Cochrane Database of Systematic Reviews 2018, Issue 8. Art. No.: CD003085
4. Devlin. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med 2018;46(9):e825-e873
A few good reviews as well
Finfer. Intravenous fluid therapy in critically ill adults. Nature Reviews Nephrology 2018;14:541–557
Bussard. Angiotensin II: a new therapeutic option for vasodilatory shock. Ther Clin Risk Manag 2018;14:1287–1298
Please drop a request for full text if needed in the comment box
Good Morning
Happy to be back on the blog
This week, we introspect about two meta analyses which analysed the outcomes associated with the use of saline versus balanced crystalloids. Balanced crystalloids are being projected and used as a safer alternative to saline which has a risk of inducing hyperchloremia.
González-Castro. Meta-analysis of the effects of normal saline on mortality in intensive care. Rev Esp Anestesiol Reanim 2018;epublished August 9th
and
Yazan. Balanced crystalloids versus isotonic saline in critically ill patients: systematic review and meta-analysis. J Intensive Care 2018;6:51
The first meta analysis looked at 8 RCTs involving more than 20000 patients. This meta analysis included studies which had mortality as the primary end point. The authors report a significant increase in mortality with the use of Saline although the OR is 1.0972. Other surrogate outcomes related to length of stay and AKI did not seem to be different.
The second meta analysis also looked at nearly 19000 + patients and evaluated the effect of saline and balanced crystalloids on mortality, LOS and incidence of AKI. There did not seem to be any difference in the outcomes when saline is used in comparison to balanced crystalloids. Incidence of RRT was also not higher in the saline group.
So, the debate seems to be unresolved. However, the odds ratio for mortality in the first Meta Analysis is not overwhelmingly against saline.
My interpretation of these two studies would be
1. Saline is not as harmful as previously thought
2. Balanced crystalloids don't seem to justify the economic impact
3. Larger studies may be needed but are likely to come out with similar results.
Happy to be back on the blog
This week, we introspect about two meta analyses which analysed the outcomes associated with the use of saline versus balanced crystalloids. Balanced crystalloids are being projected and used as a safer alternative to saline which has a risk of inducing hyperchloremia.
González-Castro. Meta-analysis of the effects of normal saline on mortality in intensive care. Rev Esp Anestesiol Reanim 2018;epublished August 9th
and
Yazan. Balanced crystalloids versus isotonic saline in critically ill patients: systematic review and meta-analysis. J Intensive Care 2018;6:51
The first meta analysis looked at 8 RCTs involving more than 20000 patients. This meta analysis included studies which had mortality as the primary end point. The authors report a significant increase in mortality with the use of Saline although the OR is 1.0972. Other surrogate outcomes related to length of stay and AKI did not seem to be different.
The second meta analysis also looked at nearly 19000 + patients and evaluated the effect of saline and balanced crystalloids on mortality, LOS and incidence of AKI. There did not seem to be any difference in the outcomes when saline is used in comparison to balanced crystalloids. Incidence of RRT was also not higher in the saline group.
So, the debate seems to be unresolved. However, the odds ratio for mortality in the first Meta Analysis is not overwhelmingly against saline.
My interpretation of these two studies would be
1. Saline is not as harmful as previously thought
2. Balanced crystalloids don't seem to justify the economic impact
3. Larger studies may be needed but are likely to come out with similar results.
Friday, August 3, 2018
Tuesday, July 17, 2018
Friday, July 13, 2018
Good Afternoon.
Burns management has always been a difficult zone for intensivists. Resuscitation and maintenance of hemodynamic stability seems to be a tight rope walk. There is no definite conclusion on "how much fluid is too much fluid" in Burns management. The concept of GIPS is particularly valid during management of severe Burns.
This week we review a study on using a novel technique for optimum management of fluid therapy during Burns management.
An objective measure for the assessment and management of fluid shifts in acute major burns
Kenworthy et al. Burns & Trauma (2018) 6:3
Kenworthy et al evaluated the role of Bio Impedance Spectroscopy in identifying the volume status of patients presenting within 48 hrs of sustaining burn injuries greater than 15%. The investigators also attempted to factor in the dressings which are employed to cover the burn area. This was an observational study carried out over two years. it is a small cohort of 21 patients. The resuscitation fluid of choice was Ringer Lactate and the target was to maintain a urine output 0.5–1.0 ml/kg/h for the first 36–48 h after burn injury.
Quantum of fluid was decided by the Parkland formula. Resistance patterns showed a significant decrease with increasing fluid. Fluid therapy was reflected in a minute to minute increase in Intra-cellular and Total Body Fluids. The percentage of burns also correlated well with the change in the resistance patterns. The investigators found that when a patient’s initial TBF increased by 1 L, R0 (Resistance at 0 frequency) decreased by 5.78 Ω (p < 0.01), R i ( intra cellular frequency) decreased 28.79 Ω (p < 0.01) and R inf (Resistance at infinite frequency) decreased 5.31 Ω (p < 0.01). A calculator was developed to identify the change in parameters due to the dressing applied.
This study seems to have identified a reliable marker of fluid characteristics and overload in Burns situation. The novelty of this study seems to be the ability to correlate the impedance characteristics real time in a minute to minute capture. The effect of the burns dressing was significant and needed to be interpreted with correction.
My comments:
1. BIS seems to be able to provide some answers to the eternal question of when to stop fluid resuscitation
2. It has given a direction for a targeted resuscitation of Burns without causing harm
3. Centres which deal with Burns on regular basis could try this method out to provide some guidance to the others.
Burns management has always been a difficult zone for intensivists. Resuscitation and maintenance of hemodynamic stability seems to be a tight rope walk. There is no definite conclusion on "how much fluid is too much fluid" in Burns management. The concept of GIPS is particularly valid during management of severe Burns.
This week we review a study on using a novel technique for optimum management of fluid therapy during Burns management.
An objective measure for the assessment and management of fluid shifts in acute major burns
Kenworthy et al. Burns & Trauma (2018) 6:3
Kenworthy et al evaluated the role of Bio Impedance Spectroscopy in identifying the volume status of patients presenting within 48 hrs of sustaining burn injuries greater than 15%. The investigators also attempted to factor in the dressings which are employed to cover the burn area. This was an observational study carried out over two years. it is a small cohort of 21 patients. The resuscitation fluid of choice was Ringer Lactate and the target was to maintain a urine output 0.5–1.0 ml/kg/h for the first 36–48 h after burn injury.
Quantum of fluid was decided by the Parkland formula. Resistance patterns showed a significant decrease with increasing fluid. Fluid therapy was reflected in a minute to minute increase in Intra-cellular and Total Body Fluids. The percentage of burns also correlated well with the change in the resistance patterns. The investigators found that when a patient’s initial TBF increased by 1 L, R0 (Resistance at 0 frequency) decreased by 5.78 Ω (p < 0.01), R i ( intra cellular frequency) decreased 28.79 Ω (p < 0.01) and R inf (Resistance at infinite frequency) decreased 5.31 Ω (p < 0.01). A calculator was developed to identify the change in parameters due to the dressing applied.
This study seems to have identified a reliable marker of fluid characteristics and overload in Burns situation. The novelty of this study seems to be the ability to correlate the impedance characteristics real time in a minute to minute capture. The effect of the burns dressing was significant and needed to be interpreted with correction.
My comments:
1. BIS seems to be able to provide some answers to the eternal question of when to stop fluid resuscitation
2. It has given a direction for a targeted resuscitation of Burns without causing harm
3. Centres which deal with Burns on regular basis could try this method out to provide some guidance to the others.
Sunday, July 8, 2018
Some new articles.
- Levy B et al Epinephrine Versus Norepinephrine for Cardiogenic Shock After Acute Myocardial Infarction Journal of the American College of Cardiology Volume 72, Issue 2, 10 July 2018, Pages 173-182
- main conclusion seems to be against the use of adrenaline in view of higher incidence of refractory cardiogenic shock
Sunday, July 1, 2018
Good reviews this week
- Kotfis. ICU delirium ― a diagnostic and therapeutic challenge in the intensive care unit. Anaesthesiol Intensive Ther 2018;50(2):160-167
- Van der Mullen. Assessment of hypovolaemia in the critically ill. Anaesthesiol Intensive Ther 2018;50(2):141-149
- Bauer. Deterioration of Organ Function As a Hallmark in Sepsis: The Cellular Perspective. Front Immunol 2018;9:1460
- Gupta. ECMO in Poisoning. J Card Crit Care 2017;1(02):82-88
Please mention your email ID in the comments if you need the full text with serial no.
Good Morning
This week we discuss an article discussing the role of microcirculatory dysfunction in traumatic hemorrhage
Although microcirculation is a focal point in most discussions on sepsis, its role in other forms of shock is discussed less often.
Microcirculatory Impairment Is Associated With Multiple Organ Dysfunction Following Traumatic Hemorrhagic Shock: The MICROSHOCK Study
Hutchings et al CCM JUNE 27 2018.
This study carried out in three major trauma centres in the UK attempted to study the pattern of microcirculatory dysfunction in traumatic hemorrhage and tried to identify a threshold for the prediction of MODS. The time points of interest were Day 0 ( within 12 hrs of hemostasis) D0 + 24 hrs and D0 + 48 hrs. Hyperlactatemia and invasive ventilatory support were part of the inclusion criteria. Incident Dark Field Videomicroscopy was used for assessment of the sublingual microcirculation. Cardiac output was measured using oesophageal doppler.
The main findings seem to suggest that microcirculatory parameters like Total Vessel Density, Perfused Vessel Density and Microcirculatory flow index showed better ROC values for predicting worsening SOFA scores than Cardiac index. Systolic Blood pressure showed the least ROC characteristics. Perfused Vessel Density showed the best discriminatory ability. This discriminatory ability persisted throughout all time points of interest.
What I learnt from the study?
1. Shock is a unique pathophysiological state irrespective of etiology
2. Microcirculatory derangements probably occur before microcirculatory changes
3. Targeting systolic blood pressure alone may delay attention to tissue hypoperfusion
4. Assessment of microcirculation may become standard of care in future
Tuesday, June 26, 2018
ICU literature review
No significant RCTs to analyse this week
However, some very good reviews
1. A state of the art review on optimal practices to prevent, recognize, and manage complications associated with intravascular devices in the critically ill.
Timsit, JF., Rupp, M., Bouza, E. et al. Intensive Care Med (2018) 44: 742
2. Diagnostic workup, etiologies and management of acute right ventricle failure
Vieillard-Baron, A., Naeije, R., Haddad, F. et al. Intensive Care Med (2018) 44: 774.
3. Expert statement for the management of hypovolemia in sepsis.
Perner, A., Cecconi, M., Cronhjort, M. et al. Intensive Care Med (2018) 44: 791
However, some very good reviews
1. A state of the art review on optimal practices to prevent, recognize, and manage complications associated with intravascular devices in the critically ill.
Timsit, JF., Rupp, M., Bouza, E. et al. Intensive Care Med (2018) 44: 742
2. Diagnostic workup, etiologies and management of acute right ventricle failure
Vieillard-Baron, A., Naeije, R., Haddad, F. et al. Intensive Care Med (2018) 44: 774.
3. Expert statement for the management of hypovolemia in sepsis.
Perner, A., Cecconi, M., Cronhjort, M. et al. Intensive Care Med (2018) 44: 791
Tuesday, June 19, 2018
Review on the Eolia trial - posted by Dr Ketan Kargirwar
Clinical Question ▪ In patients with severe ARDS, does the early initiation of Extracorporeal Membrane Oxygenation (ECMO), compared to standard care, improve mortality at day 60.
Highlight of Trial
▪ The trial was conducted with sequential design methodology according to the triangular test.
▪ Triangular test designs have the advantage of allowing a study to be stopped early either for efficacy or for futility.
▪ The stopping rules were defined prior to the commencement of the trial. The trial could be stopped due to: ▪ Safety ▪ Efficacy ▪ Futility (ie unlikely to reach a definitive result)
▪ The data safety monitoring board (DSMB) recommended stopping the trial after the 4th interim analysis 249/331 (75% of planned recruitment) when it met the predefined stopping rules for futility. ▪ A post hoc rank preserving structural failure time analysis was performed to adjust for high rate of crossover in the control group in the estimation of the “actual and unbiased” ECMO effect on survival.
Outcome
▪ Primary outcome: No statistical difference in mortality at day 60 ▪ ECMO group 44/124 (35%) vs Control group 57/125 (46%) ▪ Relative risk, 0.76; 95% confidence interval [CI], 0.55 to 1.04; P=0.09 ▪
▪ Secondary outcomes: ▪ Compared to control group, the ECMO group had:
▪ Lower relative risk of treatment failure 0.62 (95% CI, 0.47 to 0.82; P<0.001) ▪ Treatment failure was defined as death by day 60 in patients in the ECMO group, and as crossover to ECMO or death in patients in the control group
▪ Lower risk of Renal replacement therapy (RRT) at day 60 (50 vs. 32 days; median difference, 18 days; 95% CI, 0 to 51)
▪ Underwent less proning (59 vs. 46 days; median difference, 13 days; 95% CI, 5 to 59)
▪ Cross over to ECMO occurred in 35/125 (28%) of control patients ▪ Occurred at median 4 days (IQR 1 to 7) ▪ Median PaO2:FiO2 51 mmHg (IQR 46 to 61), median SaO2 77% (IQR 74 to 87), median lactate was 3.2 mmol/L (1.5-6.2) ▪ 9 patients had cardiac arrest, 7 had right heart failure, 11 received RRT ▪ 7 underwent venoarterial (VA) ECMO (and 6 had E-CPR)
▪ 60 day mortality was higher in cross over patients than rest of controls: 20/35 (57%) in cross over patients vs 90 (41%) in remaining cross over patients ▪ The hazard ratio for death within 60 days, for the ECMO group compared to controls after adjusting for selective crossover with the rank-preserving structural failure time analysis, was 0.51 (95% CI, 0.24 to 1.02; P=0.055) ▪
Weaknesses ▪ Underpowered to answer the trial question.
▪ Trial was stopped early at 249/331 (75% of recruitment) due to predefined futility rules (ie unlikely to get a definitive result.
▪ Initial power calculation was based on a 60% mortality in the control group, which became clear was inflated compared to the actual mortality rate in the controls of 46%.
▪ A 20% absolute risk reduction sets a very large requirement for a single ICU intervention, increasing the risk of a falsely negative trial (CESAR, published in 2009, had a ARR of 16%)
▪ High cross over rate of controls
▪ The 28% cross over rate resulted a reduction of separation between the two arms, and diluted the ECMO treatment effect. This potentially impacted the trial in the following ways:
▪ The cross over complicates the interpretation of the two arms in an intention to treat analysis.
▪ It also introduces a potential bias against the ECMO group in the secondary risk of treatment failure analysis, as ECMO was initiated much later and in sicker patients than the rest of the controls
▪ Despite the use of objective criteria, the decision to crossover controls to ECMO was ultimately at the discretion of unblinded treating clinicians
▪ Equipoise – high cross over rate raises the question whether some clinicians had clinical equipoise ▪ Lack of blinding of clinicians and patients/families (however difficult in such a trial)
▪ Slow recruitment of 249 patients over 6 years, leading to potential trial fatigue and/or change of practice.
▪ Expertise of ECMO centers not clearly defined ▪ Importance of VV ECMO configuration is uncertain (i.e. femoral-jugular versus femoral-femoral approach)
▪ Majority of ARDS patients in this trial were male and had pneumonia and septic shock. Extrapolation to other ARDS patient groups is uncertain
▪ The trial does not distinguish between the use of VV ECMO and VA ECMO. In particular, 7 cross over control patients underwent VA ECMO for cardiac arrest
Will EOLIA change my practise of ECMO in ARDS : There is no right or wrong answer !!! but, we should continue to use ECMO for clinical benefit in selected group of patients with the help of experts and dedicated ECMO centre as a rescue therapy in severe ARDS patients. The result of the trial produce equipoise among the clinicians due to crossover of patients. However until now there is very less data on this intervention in ARDS patients and it might be difficult to conduct another new large RCT in near future to rule out this uncertainty. Also with the diversity in practices of ECMO all over the world and with evolving technology of ECMO there is substantial consensus around use of early ECMO in ARDS.
Dr Ketan kargirwar
Clinical Question ▪ In patients with severe ARDS, does the early initiation of Extracorporeal Membrane Oxygenation (ECMO), compared to standard care, improve mortality at day 60.
Highlight of Trial
▪ The trial was conducted with sequential design methodology according to the triangular test.
▪ Triangular test designs have the advantage of allowing a study to be stopped early either for efficacy or for futility.
▪ The stopping rules were defined prior to the commencement of the trial. The trial could be stopped due to: ▪ Safety ▪ Efficacy ▪ Futility (ie unlikely to reach a definitive result)
▪ The data safety monitoring board (DSMB) recommended stopping the trial after the 4th interim analysis 249/331 (75% of planned recruitment) when it met the predefined stopping rules for futility. ▪ A post hoc rank preserving structural failure time analysis was performed to adjust for high rate of crossover in the control group in the estimation of the “actual and unbiased” ECMO effect on survival.
Outcome
▪ Primary outcome: No statistical difference in mortality at day 60 ▪ ECMO group 44/124 (35%) vs Control group 57/125 (46%) ▪ Relative risk, 0.76; 95% confidence interval [CI], 0.55 to 1.04; P=0.09 ▪
▪ Secondary outcomes: ▪ Compared to control group, the ECMO group had:
▪ Lower relative risk of treatment failure 0.62 (95% CI, 0.47 to 0.82; P<0.001) ▪ Treatment failure was defined as death by day 60 in patients in the ECMO group, and as crossover to ECMO or death in patients in the control group
▪ Lower risk of Renal replacement therapy (RRT) at day 60 (50 vs. 32 days; median difference, 18 days; 95% CI, 0 to 51)
▪ Underwent less proning (59 vs. 46 days; median difference, 13 days; 95% CI, 5 to 59)
▪ Cross over to ECMO occurred in 35/125 (28%) of control patients ▪ Occurred at median 4 days (IQR 1 to 7) ▪ Median PaO2:FiO2 51 mmHg (IQR 46 to 61), median SaO2 77% (IQR 74 to 87), median lactate was 3.2 mmol/L (1.5-6.2) ▪ 9 patients had cardiac arrest, 7 had right heart failure, 11 received RRT ▪ 7 underwent venoarterial (VA) ECMO (and 6 had E-CPR)
▪ 60 day mortality was higher in cross over patients than rest of controls: 20/35 (57%) in cross over patients vs 90 (41%) in remaining cross over patients ▪ The hazard ratio for death within 60 days, for the ECMO group compared to controls after adjusting for selective crossover with the rank-preserving structural failure time analysis, was 0.51 (95% CI, 0.24 to 1.02; P=0.055) ▪
Weaknesses ▪ Underpowered to answer the trial question.
▪ Trial was stopped early at 249/331 (75% of recruitment) due to predefined futility rules (ie unlikely to get a definitive result.
▪ Initial power calculation was based on a 60% mortality in the control group, which became clear was inflated compared to the actual mortality rate in the controls of 46%.
▪ A 20% absolute risk reduction sets a very large requirement for a single ICU intervention, increasing the risk of a falsely negative trial (CESAR, published in 2009, had a ARR of 16%)
▪ High cross over rate of controls
▪ The 28% cross over rate resulted a reduction of separation between the two arms, and diluted the ECMO treatment effect. This potentially impacted the trial in the following ways:
▪ The cross over complicates the interpretation of the two arms in an intention to treat analysis.
▪ It also introduces a potential bias against the ECMO group in the secondary risk of treatment failure analysis, as ECMO was initiated much later and in sicker patients than the rest of the controls
▪ Despite the use of objective criteria, the decision to crossover controls to ECMO was ultimately at the discretion of unblinded treating clinicians
▪ Equipoise – high cross over rate raises the question whether some clinicians had clinical equipoise ▪ Lack of blinding of clinicians and patients/families (however difficult in such a trial)
▪ Slow recruitment of 249 patients over 6 years, leading to potential trial fatigue and/or change of practice.
▪ Expertise of ECMO centers not clearly defined ▪ Importance of VV ECMO configuration is uncertain (i.e. femoral-jugular versus femoral-femoral approach)
▪ Majority of ARDS patients in this trial were male and had pneumonia and septic shock. Extrapolation to other ARDS patient groups is uncertain
▪ The trial does not distinguish between the use of VV ECMO and VA ECMO. In particular, 7 cross over control patients underwent VA ECMO for cardiac arrest
Will EOLIA change my practise of ECMO in ARDS : There is no right or wrong answer !!! but, we should continue to use ECMO for clinical benefit in selected group of patients with the help of experts and dedicated ECMO centre as a rescue therapy in severe ARDS patients. The result of the trial produce equipoise among the clinicians due to crossover of patients. However until now there is very less data on this intervention in ARDS patients and it might be difficult to conduct another new large RCT in near future to rule out this uncertainty. Also with the diversity in practices of ECMO all over the world and with evolving technology of ECMO there is substantial consensus around use of early ECMO in ARDS.
Dr Ketan kargirwar
Monday, June 18, 2018
Good Reviews.
Please post your mail ID if you need the PDF
Stolmeijer. A Systematic Review of the Effects of Hyperoxia in Acutely Ill Patients: Should We Aim for Less? Biomed Res Int 2018;2018:7841295
Gårdlund. Six subphenotypes in septic shock: Latent class analysis of the PROWESS Shock study. J Crit Care 2018;epublished June 8th
Ergan. How should we monitor patients with acute respiratory failure treated with noninvasive ventilation? European Respiratory Review 2018;27:170101
Please post your mail ID if you need the PDF
Stolmeijer. A Systematic Review of the Effects of Hyperoxia in Acutely Ill Patients: Should We Aim for Less? Biomed Res Int 2018;2018:7841295
Gårdlund. Six subphenotypes in septic shock: Latent class analysis of the PROWESS Shock study. J Crit Care 2018;epublished June 8th
Ergan. How should we monitor patients with acute respiratory failure treated with noninvasive ventilation? European Respiratory Review 2018;27:170101
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