Physical activity and the metabolic syndrome

Another reminder, from a review:

Physical activity has favorable effects on all components of the metabolic syndrome and on the resulting cardiovascular risk, the cornerstone in the development of cardiometabolic diseases. The quantity and the frequency of physical activity necessary to produce beneficial effects has not been defined as yet, but brisk walking is considered particularly appropriate, as it can be practiced by a large number of individuals, without any additional cost, and has a low rate of injury. The effects of exercise and leisure time physical activity extend from prevention to treatment of the various components of the metabolic syndrome, as well as to mood and quality of life.

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.

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.

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.

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.

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.

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.

Impact of a multidisciplinary sepsis team

Improved time to antibiotic delivery in this study. The team included a member of the pharmacy staff.

Via Hospital Medicine Virtual Journal Club.

Statin administration for the prevention of contrast induced nephropathy: is it the real deal or will it go the way of acetylcysteine?

Here are two studies from JACC that look promising. [1] [2]

Disappointing results for ICU telemedicine

From a recent study:

Design, Setting, and Participants  Observational pre-post study of patients treated in 8 “intervention” ICUs (7 hospitals within the US Department of Veterans Affairs health care system) during 2011-2012 that implemented TM monitoring during the post-TM period as well as patients treated in concurrent control ICUs that did not implement an ICU TM program.

Intervention  Implementation of ICU TM monitoring.

Main Outcomes and Measures  Unadjusted and risk-adjusted ICU, in-hospital, and 30-day mortality rates and ICU and hospital LOS for patients who did or did not receive treatment in ICUs equipped with TM monitoring.

Results Our study included 3355 patients treated in our intervention ICUs (1708 in the pre-TM period and 1647 in the post-TM period) and 3584 treated in the control ICUs during the same period. Patient demographics and comorbid illnesses were similar in the intervention and control ICUs during the pre-TM and post-TM periods...Implementation of ICU TM was not associated with a significant decline in ICU, in-hospital, or 30-day mortality rates or LOS in unadjusted or adjusted analyses. For example, unadjusted ICU mortality in the pre-TM vs post-TM periods were 2.9% vs 2.8% (P = .89) for the intervention ICUs and 4.0% vs 3.4% (P = .31) for the control ICUs. Unadjusted 30-day mortality during the pre-TM vs post-TM periods were 7.7% vs 7.8% (P = .91) for the intervention ICUs and 12.0% vs 10.2% (P = .08) for the control ICUs. Evaluation of interaction terms comparing the magnitude of mortality rate change during the pre-TM and post-TM periods in the intervention and control ICUs failed to demonstrate a significant reduction in mortality rates or LOS.

Transfusion thresholds and the risk of hospital associated infections

Interesting findings from a recent meta-analysis:

Data Extraction and Synthesis Twenty-one randomized trials with 8735 patients met eligibility criteria, of which 18 trials (n = 7593 patients) contained sufficient information for meta-analyses…

Results The pooled risk of all serious infections was 11.8% (95% CI, 7.0%-16.7%) in the restrictive group and 16.9% (95% CI, 8.9%-25.4%) in the liberal group. The risk ratio (RR) for the association between transfusion strategies and serious infection was 0.82 (95% CI, 0.72-0.95) with little heterogeneity (I2 = 0%; τ2 less than .0001). The number needed to treat (NNT) with restrictive strategies to prevent serious infection was 38 (95% CI, 24-122). The risk of infection remained reduced with a restrictive strategy, even with leukocyte reduction (RR, 0.80 [95% CI, 0.67-0.95]). For trials with a restrictive hemoglobin threshold of less than 7.0 g/dL, the RR was 0.82 (95% CI, 0.70-0.97) with NNT of 20 (95% CI, 12-133). With stratification by patient type, the RR was 0.70 (95% CI, 0.54-0.91) in patients undergoing orthopedic surgery and 0.51 (95% CI, 0.28-0.95) in patients presenting with sepsis. There were no significant differences in the incidence of infection by RBC threshold for patients with cardiac disease, the critically ill, those with acute upper gastrointestinal bleeding, or for infants with low birth weight.

Conclusions and Relevance Among hospitalized patients, a restrictive RBC transfusion strategy was associated with a reduced risk of health care–associated infection compared with a liberal transfusion strategy.

Update on vena caval filters

Here's a recent review.

The review covers both SVC and IVC filters.

SVC filters

Upper extremity DVT has a relatively low risk of causing PE. Moreover a significant complication rate associated with SVC filters raises the question of whether the benefits exceed the risks. From the review:

The low rate of PE and fatal PE associated with upper extremity thrombosis and the morbidity and mortality associated with SVC filters indicate that filters should not be used for upper extremity thrombosis except in the most extreme of circumstances.

IVC filters

Clinical judgment may occasionally dictate the use of an IVC filter in patients with high risk, large clot burden PEs who also have acute DVT. Low level evidence suggests that this approach may be beneficial. However, support for IVC filters based on high quality evidence is limited and at present the only well established indication is for acute proximal DVT and a contraindication to anticoagulant therapy. Here is a summary from the review:

Practice points

Vena cava filters prevent pulmonary embolism.

Vena cava filters increase the risk for deep venous thrombosis and vena cava thrombosis.

The only guideline approved indication for vena cava filter placement is prevention of pulmonary embolism in patients with known DVT and contraindication to anticoagulation.

Optional vena cava filters are preferred for most patients unless they have a permanent contraindication to anticoagulation and their risk for thromboembolism is persistent.

Optional vena cava filters should be removed whenever they are no longer indicated. Physicians and hospitals need to implement programs to follow patients with optional filters in order to optimize filter retrieval rates.

Work up and secondary prevention after ischemic stroke

Here is an excellent free full text review in Circulation.

A few important points from the review:

Initial imaging localizes the ischemic lesion and may identify the culprit artery.
Such imaging consists of MRI, MRA, CTA, carotid ultrasound, some combination thereof.


This initial evaluation allows placement of the ischemic stroke into one of several categories:

Based on the results of the initial neuroimaging studies, the stroke can be classified into preliminary diagnostic categories: large vessel occlusion, small vessel occlusion, potential cardioembolic, or unknown/other.


Small vessel strokes, aka lacunar strokes are defined by size (under 15 mm diameter) and subcortical location.

Secondary prevention in these cases involves antiplatelet therapy and management of vascular risk factors.


If no large artery culprit is identified, the stroke is not lacunar and the patient is not in atrial fibrillation then further investigation for a cardioembolic source is indicated.

This will consist of further monitoring for atrial fibrillation as well as TTE and/or TEE.


Intracranial large vessel stenosis is managed with antiplatelet therapy and standard risk factor modification.

Systemic anticoagulation and mechanical revascularization have not proven favorable in clinical trials.


Many patients with so called cryptogenic strokes are later found to have paroxysmal atrial fibrillation.


Outpatient event monitoring is recommended for patients whose strokes are considered cryptogenic at discharge.

Recommendations for duration of monitoring vary. The review author says at least two weeks.


Extensive thrombophilia testing is not recommended.


Mitral valve prolapse is no longer considered an important cause of cryptogenic stroke.


PFO management for secondary stroke prevention remains controversial.

High level studies do not support any special approach (systemic anticoagulation, closure) for most patients.

Stanford Medicine 25

A teaching web site and blog dedicated to the culture of bedside medicine. Great educational content.

Effects of target specific (novel) oral anticoagulants on the coag assays

Quantitative monitoring or TSOACs is not available in most community hospitals nor is it necessary. Nevertheless some knowledge of the qualitative effects of these agents on commonly used assays may come in handy to assess for “drug on board” or to get some idea of excessive effect and bleeding risk. The information below was taken from this resource.

For dabigatran, the aPTT may provide a qualitative assessment of dabigatran level and activity. The relation between dabigatran and the aPTT is curvilinear (Figure 3).12 Nevertheless, the sensitivity of the different aPTT reagents varies greatly. In patients receiving chronic therapy with dabigatran 150 mg twice daily (bid), the median peak aPTT was approximately two-fold that of control. Twelve hours after the last dose, the median aPTT was 1.5-fold that of control, with less than 10% of patients exhibiting two-fold increases. Therefore, if the aPTT level at trough (i.e. 12–24 h after ingestion) still exceeds two times the upper limit of normal, this may be associated with a higher risk of bleeding, and may warrant caution especially in patients with bleeding risk factors.12

Dabigatran has little effect on the PT and INR at clinically relevant plasma concentrations, resulting in a very flat response curve...

Factor Xa-inhibitors demonstrate a concentration-dependent prolongation of the PT. Nevertheless the effect on the PT depends both on the assay and on the FXa inhibitor. For rivaroxaban, the PT may provide some quantitative information, even though the sensitivity of the different PT reagents varies greatly (Figure 4). If Neoplastin Plus or Neoplastin is used as thromboplastin reagent, the PT is influenced in a dose-dependent manner with a close correlation to plasma concentrations.16 Neoplastin Plus is also more sensitive than Neoplastin.14 Assay-specific calibrators and calibration curves can be made (Figure 4). There are currently no such data available for edoxaban and apixaban. Importantly, the INR (and certainly a point-of-care determined INR) is completely unreliable for the evaluation of FXa inhibitory activity.

Finally it should be noted that the TSOACs can interfere with thrombophilia tests.

Type B lactic acidosis

A nice discussion over at Renal Fellow Network.

Classically, Type A lactic acidosis is related to tissue hypoperfusion resulting in an increase in anaerobic glycolysis. Type B lactic acidosis occurs despite the presence of sufficient oxygen for aerobic glycolysis. There are a number of important causes..

TNF inhibitors: what the hospitalist needs to know

Free full text from CCJM.

New oral anticoagulants in the treatment of DVT and PE

This editorial contains a rundown of the phase III trials for all four agents that have been studied. It is available as free full text. Key points:

...First, all DOACs were shown consistently to be non-inferior compared with well-managed warfarin. The high quality of warfarin management, with a superior time in international normalized ratio target range compared with daily clinical practice, strengthens both the internal and external validity of these studies but also underscores that well-managed warfarin is an effective therapy for preventing recurrent VTE...

To me the time in therapeutic range for warfarin was not that great in those trials. However, you can be sure it was better than it is in the community.

Second, all DOACs caused less bleeding. Importantly, the shift in the bleeding pattern that is observed in patients with atrial fibrillation, with less intracranial, less life-threatening, and less critical site bleedings, is also seen in patients with VTE. DOACs cause less major (Table) and less intracranial bleedings in patients with VTE, but caution remains, in particular for patients at risk for gastrointestinal bleeding.

Third, the new regimens differ in their initial treatment approach. The first couple of weeks are of particular interest because of the high risk for recurrence and bleeding. The dual-drug bridging period with overlapping heparin and vitamin K antagonists constitutes a risk for overtreatment and undertreatment and requires intensive international normalized ratio monitoring that is labor- and time-consuming and costly. Furthermore, lessons have been drawn from the observation that ximelagatran9 and idraparinux,10 administered without heparin lead-in and without initial intensified dosing, caused more early recurrence compared with heparin/vitamin K antagonists. This helps to explain the 2 different strategies of DOACs for acute VTE (ie, including a heparin lead-in or starting with an intensified dose)...

Parenteral heparin will remain a preferred treatment option for many patients, especially those with more severe clinical presentations and patients with high thrombus burden who are admitted to the hospital. When parenteral heparin has been administered for 5 to 10 days, peroral anticoagulation with dabigatran or edoxaban can be continued.

For most cancer patients, the continued treatment with LMWH is currently the recommended and preferred therapy. Patients with active cancer for whom long-term treatment with LMWH was anticipated were not eligible for the phase III trials. Hence, additional studies are needed in cancer patients with continued LMWH and not warfarin as the comparator before DOACs can be considered an alternative standard to continued LMWH in these patients...

Besides particular patient characteristics, also less common clinical manifestations of VTE require our attention. DOACs have only been studied in patients with proximal DVT of the lower limb or hemodynamically stable pulmonary embolism. Patients with distal DVT, DVT of the upper limb, superficial thrombophletitis, or catheter-related thrombosis, patients who underwent thrombolysis, and patients with cerebral vein or mesenteric vein thrombosis have not been studied yet.

Remember thrombotic storm?

A while back I blogged about this condition.

It's essentially what the name implies. There is no known single substrate nor is there a known single trigger (a number of patients seem to have had infection). Very few patients had known hereditary thrombophilia. Some had antipholpholipid syndrome and catastrophic APLS may be a subset of TS. It is defined clinically and likely represents a variety of (as yet undiscovered?) underlying disorders.

Despite a probable diversity of underlying hypercoagulable disorders TS is emerging as a clinically distinct entity. Since the above posting investigators have gotten more organized, and there are now more resources available regarding the condition which can be accessed here and here.