Tuesday, July 29, 2014

Meta-analysis of prone ventilation for severe ARDS

From the paper:

Data Synthesis:This analysis included 11 randomized controlled trial, 2,246 total adult patients, and 1,142 patients ventilated in the prone position. Prone positioning during ventilation significantly reduced overall mortality in the random-effect model (odds ratio, 0.77; 95% CI, 0.59–0.99; p = 0.039; I2 = 33.7%), and the effects were marked in the subgroup in which the duration of prone positioning was more than 10 hr/session, compared with the subgroup with a short-term duration of prone positioning (odds ratio, 0.62; 9% CI, 0.48–0.79; p = 0.039; pinteraction = 0.015). Prone positioning was significantly associated with pressure ulcers (odds ratio, 1.49; 95% CI, 1.18–1.89; p = 0.001; I2 = 0.0%) and major airway problems (odds ratio, 1.55; 95% CI, 1.10–2.17; p = 0.012; I2 = 32.7%).
Conclusions:Ventilation in the prone position significantly reduced overall mortality in patients with severe acute respiratory distress syndrome. Sufficient duration of prone positioning was significantly associated with a reduction in overall mortality. Prone ventilation was also significantly associated with pressure ulcers and major airway problems.

Monday, July 28, 2014

How low can you go? Evaluating the trigger for a restrictive transfusion strategy

From a recent systematic review and meta-analysis:

Results
In the primary analysis, pooled results from 3 trials with 2364 participants showed that a restrictive hemoglobin transfusion trigger of less than 7 g/dL resulted in reduced in-hospital mortality (risk ratio [RR], 0.74; confidence interval [CI], 0.60-0.92), total mortality (RR, 0.80; CI, 0.65-0.98), rebleeding (RR, 0.64; CI, 0.45-0.90), acute coronary syndrome (RR, 0.44; CI, 0.22-0.89), pulmonary edema (RR, 0.48; CI, 0.33-0.72), and bacterial infections (RR, 0.86; CI, 0.73-1.00), compared with a more liberal strategy. The number needed to treat with a restrictive strategy to prevent 1 death was 33. Pooled data from randomized trials with less restrictive transfusion strategies showed no significant effect on outcomes.
Conclusions
In patients with critical illness or bleed, restricting blood transfusions by using a hemoglobin trigger of less than 7 g/dL significantly reduces cardiac events, rebleeding, bacterial infections, and total mortality. A less restrictive transfusion strategy was not effective.

Observational studies on patients with very low hemoglobin concentrations (5 or 6) who are normovolemic show that they tolerate it well. Compensatory mechanisms for the anemia are cited:

A systematic review found consistent evidence that normovolemic anemia is associated with a reduction in systemic vascular resistance and an increase in cardiac output, coronary and cerebral blood flow, and synthesis of 2,3-diphosphoglycerate in red blood cells, resulting in maintenance of oxygen delivery and extraction.

Increased red cell 2,3 DPG levels shifts the oxy-hemoglobin dissociation curve to the right, making hemoglobin less stingy. Transfused red cells on the other hand may have decreased 2,3 DPG levels as a result of storage.

Improved outcomes with a restrictive strategy were seen across the board, including two groups of particular interest: acute bleeding and coronary artery disease.

Here is a recent study showing improved outcomes with a restrictive strategy in patients with GI bleeding.

Related editorial here.

My institution has adopted a restrictive transfusion strategy, leveraged by the EMR. It has worked, as evidenced by the number of frantic calls I get from nursing personnel, triggered by very low H&H levels on morning labs.

Sunday, July 27, 2014

SARS versus MERS

From a recent review:

Recent findingsBats are the natural reservoirs of SARS-like coronaviruses (CoVs) and are likely the reservoir of MERS coronavirus (MERS-CoV). Although a small number of camels have been found to have positive nasal swabs by real-time polymerase chain reaction and to carry antibody against MERS-CoV, the transmission route and the intermediary animal source remain uncertain amongst the sporadic primary cases. Both SARS-CoV and MERS-CoV may cause severe respiratory failure and extrapulmonary features such as diarrhoea, whereas mild or asymptomatic cases also occur in both conditions. In comparison with SARS, patients with MERS are older with male predominance, more comorbid illness and relatively lower human-to-human transmission potential. Although the viral kinetics of MERS-CoV remain unknown, nosocomial infections of MERS occur early within the first week of illness of the index case, whereas those of SARS occurred mainly in the second week of illness when the patient's upper airway viral load peaks on day 10 of illness. In-vitro data suggest that interferon (IFN) with or without ribavirin and mycophenolic acid may inhibit MERS-CoV, whereas protease inhibitors and IFN have inhibitory activity against SARS-CoV.

SummaryAlthough there are some similarities in the clinical features, MERS progresses to respiratory failure much more rapidly than SARS. The higher case fatality rate of MERS is likely related to older age and comorbid illness. More studies are needed to understand MERS-CoV in order to guide public health infection control measures and treatment.

Saturday, July 26, 2014

Effect of a transitions program on readmission

From AJHSP:

Results Over the 2-year study period, 19,659 unique patients had 26,781 qualifying index admissions, 2,523 of which resulted in a readmission within 30 days of discharge. After adjusting for various demographic and clinical characteristics, the usual care group (i.e., patients who did not participate in the program) had nearly twice the odds of readmission within 30 days (odds ratio [OR], 1.90; 95% confidence interval [CI], 1.35–2.67), compared with the intervention group (i.e., program participants). For patients age 65 years or older, those in the usual care group had a sixfold increase in the odds of a 30-day readmission (OR, 6.05; 95% CI, 1.92–19.00) relative to those in the intervention group.

Via Hospital Medicine Virtual Journal Club.

Uric acid as a risk factor for erectile dysfunction

In this study there was a two fold increase in risk of ED for every 1 mg/dL increase in uric acid.

HT to Clinical Cases and Images.


Thursday, July 24, 2014

IVC filters for patients with unstable pulmonary embolism

PE of such severity that another one is likely to be fatal has been a popular, though not strictly evidence based, indication for IVC filter insertion. However accumulating lower level evidence and opinion increasingly favor such use. Here's such an opinion recently published in the American Journal of Medicine.

Wednesday, July 23, 2014

Sedation in mechanically ventilated patients

Here's a trial comparing daily interruption of continuous infusion sedation with prn sedation. From the study:

Methods
Adult patients expected to need mechanical ventilation for more than 24 hours were randomly assigned, in a single center, either to daily interruption of continuous sedative and opioid infusion or to intermittent sedation. In both cases, our goal was to maintain a Sedation Agitation Scale (SAS) level of 3 or 4; that is patients should be calm, easily arousable or awakened with verbal stimuli or gentle shaking. Primary outcome was ventilator-free days in 28 days. Secondary outcomes were ICU and hospital mortality, incidence of delirium, nurse workload, self-extubation and psychological distress six months after ICU discharge.

Results
A total of 60 patients were included. There were no differences in the ventilator-free days in 28 days between daily interruption and intermittent sedation (median: 24 versus 25 days, P = 0.160). There were also no differences in ICU mortality (40 versus 23.3%, P = 0.165), hospital mortality (43.3 versus 30%, P = 0.284), incidence of delirium (30 versus 40%, P = 0.472), self-extubation (3.3 versus 6.7%, P = 0.514), and psychological stress six months after ICU discharge. Also, the nurse workload was not diPatients in the intermittent sedation group would be kept without continuous infusion of sedatives if the intubation had been performed in the ICU, or would have their infusion interrupted after randomization if they had been admitted already intubated from emergency department, surgical room, wards or another ICU. Patients would be kept without sedatives infusion until they awoke. After patients were awake, if they were calm and collaborative (SAS of 4), they would be kept without infusion of sedatives. If the patient was uncomfortable or agitated (SAS greater then or equal to 5), the physician (attending or resident) would be consulted, and possible causes of discomfort would be investigated in a standardized method (pain, patient-ventilator asynchrony, thirst, hunger, and position on the bed, all of them using a poster which included figures expressing these uncomfortable sensations) and treated. Pain was treated with boluses of fentanyl (50 to 150 μg). If the pain recrudesced in less than two hours or there was a persistent pain stimulus (for example, surgical scar, drains) a continuous infusion of fentanyl would be initiated and titrated by the attending nurse using numeric pain scale (which measures pain from 0 = no pain, to 10 = the worst pain ever experienced) aiming a value less than or equal to 4. If agitation had no visible cause and pain was already empirically treated with a bolus of fentanyl, then delirium would be suspected and haloperidol administrated (bolus of 2.5 or 5 mg). After 15 minutes, if the patient was still uncomfortable or agitated, a continuous infusion of midazolam or propofol would be initiated to achieve a SAS of 3 to 4. The choice between midazolam and propofol was at the discretion of the attending physician. Sedative dosing would be titrated every two hours thereafter or sooner if the patient was agitated (that is, SAS greater than or equal to 5). Interruption of sedatives infusions would then be performed during the next shift (morning, afternoon or night) in order to try to keep the patient without sedation again.fferent between groups, but it was reduced on day 5 compared to day 1 in both groups (Nurse Activity Score (NAS) in the intermittent sedation group was 54 on day 1 versus 39 on day 5, P less than 0.001; NAS in daily interruption group was 53 on day 1 versus 38 on day 5, P less than 0.001). Fentanyl and midazolam total dosages per patient were higher in the daily interruption group. The tidal volume was higher in the intermittent sedation group during the first five days of ICU stay. 

Conclusions
There was no difference in the number of ventilator-free days in 28 days between both groups. Intermittent sedation was associated with lower sedative and opioid doses.

Prior research cited in the paper yielded similar results. In looking at the accumulating experience it appears that the less sedation given the better. No sedation at all may be best for those patients who can tolerate it.

The protocol for the prn sedative group is noteworthy. Again, from the paper:

Patients in the intermittent sedation group would be kept without continuous infusion of sedatives if the intubation had been performed in the ICU, or would have their infusion interrupted after randomization if they had been admitted already intubated from emergency department, surgical room, wards or another ICU. Patients would be kept without sedatives infusion until they awoke. After patients were awake, if they were calm and collaborative (SAS of 4), they would be kept without infusion of sedatives. If the patient was uncomfortable or agitated (SAS greater then or equal to 5), the physician (attending or resident) would be consulted, and possible causes of discomfort would be investigated in a standardized method (pain, patient-ventilator asynchrony, thirst, hunger, and position on the bed, all of them using a poster which included figures expressing these uncomfortable sensations) and treated. Pain was treated with boluses of fentanyl (50 to 150 μg). If the pain recrudesced in less than two hours or there was a persistent pain stimulus (for example, surgical scar, drains) a continuous infusion of fentanyl would be initiated and titrated by the attending nurse using numeric pain scale (which measures pain from 0 = no pain, to 10 = the worst pain ever experienced) aiming a value less than or equal to 4. If agitation had no visible cause and pain was already empirically treated with a bolus of fentanyl, then delirium would be suspected and haloperidol administrated (bolus of 2.5 or 5 mg). After 15 minutes, if the patient was still uncomfortable or agitated, a continuous infusion of midazolam or propofol would be initiated to achieve a SAS of 3 to 4. The choice between midazolam and propofol was at the discretion of the attending physician. Sedative dosing would be titrated every two hours thereafter or sooner if the patient was agitated (that is, SAS greater than or equal to 5). Interruption of sedatives infusions would then be performed during the next shift (morning, afternoon or night) in order to try to keep the patient without sedation again.

As illustrated above prn sedation requires a systematic, not a knee-jerk, approach to the patient involving pain control and a series of assessments for the causes of agitation, followed by bolus haloperidol before resorting to benzodiazepines or propofol.

The caveat is that this approach is not likely suitable for patients with ARDS who require low tidal volume ventilation and sometimes prone positioning and neuromuscular blockade, modalities which require continuous sedation.