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.
Sunday, September 23, 2018
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
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