Saturday, December 10, 2016

Assessment of volume responsiveness in critically ill patients

From JAMA’s Rational Clinical Examination series:

Objective To identify predictors of fluid responsiveness in hemodynamically unstable patients with signs of inadequate organ perfusion.

Data Sources and Study Selection Search of MEDLINE and EMBASE (1966 to June 2016) and reference lists from retrieved articles, previous reviews, and physical examination textbooks for studies that evaluated the diagnostic accuracy of tests to predict fluid responsiveness in hemodynamically unstable adult patients who were defined as having refractory hypotension, signs of organ hypoperfusion, or both. Fluid responsiveness was defined as an increase in cardiac output following intravenous fluid administration.

Data Extraction Two authors independently abstracted data (sensitivity, specificity, and likelihood ratios [LRs]) and assessed methodological quality. A bivariate mixed-effects binary regression model was used to pool the sensitivities, specificities, and LRs across studies.

Results A total of 50 studies (N = 2260 patients) were analyzed. In all studies, indices were measured before assessment of fluid responsiveness. The mean prevalence of fluid responsiveness was 50% (95% CI, 42%-56%). Findings on physical examination were not predictive of fluid responsiveness with LRs and 95% CIs for each finding crossing 1.0. A low central venous pressure (CVP) (mean threshold less than 8 mm Hg) was associated with fluid responsiveness (positive LR, 2.6 [95% CI, 1.4-4.6]; pooled specificity, 76%), but a CVP greater than the threshold made fluid responsiveness less likely (negative LR, 0.50 [95% CI, 0.39-0.65]; pooled sensitivity, 62%). Respiratory variation in vena cava diameter measured by ultrasound (distensibility index greater than 15%) predicted fluid responsiveness in a subgroup of patients without spontaneous respiratory efforts (positive LR, 5.3 [95% CI, 1.1-27]; pooled specificity, 85%). Patients with less vena cava distensibility were not as likely to be fluid responsive (negative LR, 0.27 [95% CI, 0.08-0.87]; pooled sensitivity, 77%). Augmentation of cardiac output or related parameters following passive leg raising predicted fluid responsiveness (positive LR, 11 [95% CI, 7.6-17]; pooled specificity, 92%). Conversely, the lack of an increase in cardiac output with passive leg raising identified patients unlikely to be fluid responsive (negative LR, 0.13 [95% CI, 0.07-0.22]; pooled sensitivity, 88%).

Conclusions and Relevance Passive leg raising followed by measurement of cardiac output or related parameters may be the most useful test for predicting fluid responsiveness in hemodynamically unstable adults. The usefulness of respiratory variation in the vena cava requires confirmatory studies.

Is simple pulse pressure measurement a reliable surrogate for CO? There is a relationship but it appears to be non linear as discussed here.

Of interest, CVP measurement had fair test characteristics. Ultrasound measurement of vena cava distensibility was of limited usefulness, and then only in mechanically ventilated patients with no spontaneous respiratory effort.

Friday, December 09, 2016

Antivirals added to steroids for treatment of Bell palsy

Clinical Question Compared with oral corticosteroids alone, are oral antiviral drugs associated with improved outcomes when combined with oral corticosteroids in patients presenting within 72 hours of the onset of Bell palsy?

Bottom Line Compared with oral corticosteroids alone, the addition of acyclovir, valacyclovir, or famcyclovir to oral corticosteroids for treatment of Bell palsy was associated with a higher proportion of people who recovered at 3- to 12-month follow-up. The quality of evidence is limited by heterogeneity, imprecision of the result estimates, and risk of bias.

AICD use in patients with non-ischemic dilated cardiomyopathy

The original use of the AICD for primary prevention of arrhythmic collapse (other than in patients with channelopathy) was in patients post MI with reduced ejection fraction as validated in the MADIT and MADIT II studies. The indications were expanded to patients with dilated cardiomyopathy of all causes after SCD-HeFT. In SCD-HeFT about half the patients had ischemic DCM and about half non-ischemic. But up to now no one had done this same study on a population composed purely of patients with non-ischemic DCM. That was the subject of this study recently published in NEJM. From the article:


The benefit of an implantable cardioverter–defibrillator (ICD) in patients with symptomatic systolic heart failure caused by coronary artery disease has been well documented. However, the evidence for a benefit of prophylactic ICDs in patients with systolic heart failure that is not due to coronary artery disease has been based primarily on subgroup analyses. The management of heart failure has improved since the landmark ICD trials, and many patients now receive cardiac resynchronization therapy (CRT).

In a randomized, controlled trial, 556 patients with symptomatic systolic heart failure (left ventricular ejection fraction, less than or equal to 35%) not caused by coronary artery disease were assigned to receive an ICD, and 560 patients were assigned to receive usual clinical care (control group). In both groups, 58% of the patients received CRT. The primary outcome of the trial was death from any cause. The secondary outcomes were sudden cardiac death and cardiovascular death.

After a median follow-up period of 67.6 months, the primary outcome had occurred in 120 patients (21.6%) in the ICD group and in 131 patients (23.4%) in the control group (hazard ratio, 0.87; 95% confidence interval [CI], 0.68 to 1.12; P=0.28). Sudden cardiac death occurred in 24 patients (4.3%) in the ICD group and in 46 patients (8.2%) in the control group (hazard ratio, 0.50; 95% CI, 0.31 to 0.82; P=0.005). Device infection occurred in 27 patients (4.9%) in the ICD group and in 20 patients (3.6%) in the control group (P=0.29).

In this trial, prophylactic ICD implantation in patients with symptomatic systolic heart failure not caused by coronary artery disease was not associated with a significantly lower long-term rate of death from any cause than was usual clinical care. (Funded by Medtronic and others; DANISH number, NCT00542945.)

But things are not as a superficial reading of the conclusion might indicate. First, if you had a device you were only half as likely to drop dead suddenly (NNT 25). Moreover, although it did not reach statistical significance the point estimate for all cause mortality in the device group was lower.

What are the implications for practice? First, before you exclude a patient with DCM from device therapy you would want to rule out coronary disease. We usually do that anyway but the guidelines give us some wiggle room. Second, for those in whom CAD is ruled out we will have to rethink device recommendations on each individual case. It can be expected, and considered appropriate, that individual clinician judgment and patient preferences will drive decision making and some degree of practice variation.

Wednesday, November 02, 2016

Skepticism about accountable care organizations

Here is a JAMA Viewpoint piece expressing a negative opinion about ACOs. (A companion article in the same issue was favorable). Key points:

The authors point out that any cost savings attributable to the ACOs appear to be nominal. Moreover they tend to be offset by the bonuses paid out to the participants. These bonuses cannot be considered optional because they are inherent to the core notion of the ACO: that “quality” will be rewarded.

The model creates incentives to integrate services. Thus smaller hospitals close or are merged, resulting in monopolies among health care delivery systems. This reduces competition and tends to drive costs up, not down.

Tuesday, November 01, 2016

Accountable care organizations: how are they working?

The authors of this JAMA Viewpoint article say the model has been a success, but the arguments are unconvincing. Here are some caveats:

The experiment is in its infancy.

Overall the results are mixed.

Cost savings have been modest and in some cases are diminishing and may prove to be transient. That's what we saw in the managed care experiment of a couple of decades ago.

Statements about quality improvement are suspect because real quality cannot be measured. Outcome data are very soft.

Monday, October 31, 2016

Multiple clinical manifestations of IgG4 related disease (IgG4-RD)

Here are some key issues addressed in a recent review.

What are some of the IgG4 related diseases?

These may coexist in the same patient:

Autoimmune pancreatitis type 1
Mikulicz disease (salivary gland infiltration)
Constrictive pericarditis
Coronary artery aneurysm
Inflammatory abdominal aortic aneurysm (and the related condition retroperitoneal fibrosis)
Sclerosing mediastinitis
Riedel's thyroiditis (and other forms of thyroid involvement)
Sclerosing mastitis
Pulmonary mass or interstitial disease
Lymphadenopathy (Castleman like and other forms)
Tubulointerstitial nephritis
Sclerosing cholangitis (which differs in some features from primary sclerosing cholangitis)

How is IgG4-RD diagnosed?

This has been in a state of some controversy and flux. From the article:

According to an international symposium held in 2011, the diagnosis of IgG4-RD requires both an appropriate histological appearance and increased numbers of IgG4-positive plasma cells (or an elevated IgG4:IgG ratio) in tissue...

In 2011, an “All Japan IgG4 Team,” with the aim to draft comprehensive diagnostic criteria for IgG4-RD 51 ( Table 3 ), proposed three major items 51 69 (1) single or multiple organs involved with diffuse or localized swelling, masses, nodules, and/or hypertrophic lesions; (2) elevated serum IgG4 levels (greater than or equal to 135 mg/dL); and (3) histopathologic features that include marked lymphocytic and plasma cell infiltration and fibrosis, with IgG4-positive plasma cell infiltration (IgG4/IgG-positive cell ratio of greater than or equal to 40% and IgG4-positive plasma cells exceeding 10/HPF). Based on these criteria, patients can be classified into the categories of definite, probable, or possible IgG4-RD.

How do autoimmune pancreatitis (AP) types 1 and 2 differ?

Age: older onset (6th decade) typical of type 1
Gender: male predominance in type 1, not 2
Relationship to IgG4: present in type 1, not clearly present in 2
Histology: lymphoplasmacytic sclerosing pancreatitis in type 1, idiopathic duct centric pancreatitis in 2
Abdominal pain: common in type 2, not in 1
Other organ involvement common in 1, not 2
Steroid responsiveness characterizes both types but type 1 is more prone to relapse.

Sunday, October 30, 2016

IgG-4 related disease overview

Here is an overview from Disease of the Month. IgG-4 diseases include one of the two types of autoimmune pancreatitis and several other conditions:

Immunoglobulin G4-related disease is a rare but increasingly recognized multisystem entity characterized by lymphoplasmacytic tissue infiltration...Related manifestations of this disease include Reidel’s thyroiditis, chronic sclerosing dacryoadenitis, autoimmune pancreatitis (type 1 AIP), retroperitoneal fibrosis, and tubulointerstitial nephritis. Usually occurring in older men, the diagnosis is primarily based upon finding of histopahtologic changes..

Saturday, October 29, 2016

High flow nasal cannula vs NIPPV post extubation

Question Is high-flow nasal cannula noninferior to noninvasive ventilation for preventing reintubation and postextubation respiratory failure?

Findings In this multicenter randomized noninferiority clinical trial that included 604 adults, the proportion requiring reintubation was 22.8% with high-flow therapy vs 19.1% with noninvasive ventilation, and postextubation respiratory failure was observed in 26.9% with high-flow therapy vs 39.8% with noninvasive ventilation, reaching the noninferiority threshold.

Meaning High-flow nasal cannula immediately after scheduled extubation was not inferior to noninvasive mechanical ventilation for risk of reintubation and postextubation respiratory failure in patients at high risk of reintubation.