Cardiac function and brain aging

We've long known about the concept of cardiac encephalopathy. That concept has been refined and now there is evidence that even mild alterations in cardiac physiology contribute to brain aging in a graded fashion.

Hemodynamic targets during induced hypothermia post arrest

From a paper in Resuscitation:

Abstract

Aim

In analogy with sepsis, current post-cardiac arrest (CA) guidelines recommend to target mean arterial pressure (MAP) above 65 mmHg and SVO2 above 70%. This is unsupported by mortality or cerebral perfusion data. The aim of this study was to explore the associations between MAP, SVO2, cerebral oxygenation and survival.

Methods

Prospective, observational study during therapeutic hypothermia (24 h – 33 °C) in 82 post-CA patients monitored with near-infrared spectroscopy.

Results

Forty-three patients (52%) survived in CPC 1–2 until 180 days post-CA. The mean MAP range associated with maximal survival was 76–86 mmHg (OR 2.63, 95%CI [1.01; 6.88], p = 0.04). The mean SVO2 range associated with maximal survival was 67–72% (OR 8.23, 95%CI [2.07; 32.68], p = 0.001). In two separate multivariate models, a mean MAP (OR 3.72, 95% CI [1.11; 12.50], p = 0.03) and a mean SVO2 (OR 10.32, 95% CI [2.03; 52.60], p = 0.001) in the optimal range persisted as independently associated with increased survival. Based on more than 1 625 000 data points, we found a strong linear relation between SVO2 (range 40–90%) and average cerebral saturation (R2 0.86) and between MAP and average cerebral saturation for MAP's between 45 and 101 mmHg (R2 0.83). Based on our hemodynamic model, the MAP and SVO2 ranges associated with optimal cerebral oxygenation were determined to be 87–101 mmHg and 70–75%.

Conclusion

we showed that a MAP range between 76–86 mmHg and SVO2 range between 67% and 72% were associated with maximal survival. Optimal cerebral saturation was achieved with a MAP between 87–101 mmHg and a SVO2 between 70% and 75%. Prospective interventional studies are needed to investigate whether forcing MAP and SVO2 in the suggested range with additional pharmacological support would improve outcome.

Shorter lengths of stay may mean higher mortality after hip fracture

This study in BMJ just dropped a bomb:

Setting Population greater than or equal to 50 years old living in Sweden as of 31 December 2005 with a first hip fracture the years 2006-12.

Participants 116 111 patients with an incident hip fracture from a closed nationwide cohort.

Main outcome measure Death within 30 days of hospital discharge in relation to hospital length of stay after adjustment for multiple covariates.

Results Mean inpatient length of stay after a hip fracture decreased from 14.2 days in 2006 to 11.6 days in 2012 (P less than 0.001). The association between length of stay and risk of death after discharge was non-linear (P less than 0.001), with a threshold for this non-linear effect of about 10 days. Thus, for patients with length of stay of less than or equal to 10 days (n=59 154), each 1-day reduction in length of stay increased the odds of death within 30 days of discharge by 8% in 2006 (odds ratio 1.08 (95% confidence interval 1.04 to 1.12)), which increased to16% in 2012 (odds ratio 1.16 (1.12 to 1.20)). In contrast, for patients with a length of stay of greater than or equal to 11 days (n=56 957), a 1-day reduction in length of stay was not associated with an increased risk of death after discharge during any of the years of follow up.

Limitations No accurate evaluation of the underlying cause of death could be performed.

Conclusion Shorter length of stay in hospital after hip fracture is associated with increased risk of death after hospital discharge, but only among patients with length of stay of 10 days or less. This association remained robust over consecutive years.

That ought to make administrators and policy makers uneasy.

ACP Hospitalist Weekly quotes this from a related editorial:

The authors of an accompanying editorial discussed the trend in modern health care toward shorter lengths of stay and said that "it is far from clear that reductions in length of stay do not cause harm."

Indeed. That's been a nagging elephant in the room in the United States ever since the Prospective Payment System went into effect in 1984. The concern has not been addressed as it should be although there is a recently emerging literature showing that short lengths of stay in heart failure patients are associated with worse outcomes.

Pulmonary complications of hereditary haemorrhagic telangiectasia

From a recent review in Current Opinion in Pulmonary Medicine:

The purpose of this study is to present the latest advances and recommendations in the diagnosis and treatment of pulmonary vascular complications associated with hereditary haemorrhagic telangiectasia (HHT): pulmonary arteriovenous malformations (PAVMs), pulmonary arterial hypertension (PAH), pulmonary hypertension associated with high output cardiac failure or liver vascular malformations, haemoptysis, haemothorax and thromboembolic disease.

Recent findings

Transthoracic contrast echocardiography has been validated as a screening tool for PAVM in patients with suspected HHT. Advancements in genetic testing support its use in family members at risk as a cost-effective measure. Therapy with bevacizumab in patients with high output cardiac failure and severe liver AVMs showed promising results. PAH tends to be more aggressive in HHT type 2 patients.

Summary

Patients suffering from this elusive disease should be referred to HHT specialized centres to ensure a standardized and timely approach to diagnosis and management.

Dextrose and insulin in the treatment of hyperkalemia

This summary from Academic Life inEmergency Medicine is a nice reference.

It makes the point that hypoglycemia following treatment is more of a hazard than is commonly recognized, and that at least hourly point of care glucose checks are necessary for a while.

Global PI village

A repository of information onprimary immune deficiencies.

Video laryngoscopy versus direct laryngoscopy for intubation during CPR

From a recent study:

Methods

This study is a historically controlled clinical design. From May 2011 to April 2013 out-of-hospital cardiac arrest patients were intubated during CPR by novice EPs. CPR data was automatically recorded by pre-installed video and subsequently analysed. The primary outcome was the success rate of the first-attempt at ETI. In addition, time to successful ETI from first-attempt (T-complete), duration of chest compression interruptions, and incidence of oesophageal intubation were compared.

Results

Of 305 patients undergoing ETI, 83 were intubated by novice EPs. The success rate of first-attempt ETI in the VL group (n = 49) was higher than that in the DL group (n = 34, 91.8% vs. 55.9%; p less than 0.001). The median T-complete was significantly shorter with VL than with DL (37 [29–55] vs. 62 [56–110] s; p less than 0.001). Oesophageal intubation was observed only in the DL group (n = 6, 17.6%). The median duration of chest compression interruptions was greater with DL (7 [3–6] s) than with VL (0 [0–0] s). Improvements in ETI during CPR were observed in the VL group after the first 3 months, but not the DL group during regular use for 1 year.

Conclusions

For novice EPs, the VL could significantly improve the first-attempt success in ETI during CPR while the DL couldn’t improve it.

Another similar study here.

Management of inpatients with cirrhosis

Via ACP Hospitalist Weekly, here are some tips from a talk given at Internal Medicine Meeting 2015.

SBP, an ever present threat

Up to a third of patients with ascites will have this on admission regardless of the reason for admission, which is why paracentesis is recommended on all patients.

The use of albumin

As quoted from the ACP Hospitalist Weekly article:

If you find SBP, treatment is 25% albumin, 1.5 g/kg on day 1 and 1 g/kg on day 3, and cefotaxime or a fluoroquinolone (unless the patient was already on a fluoroquinolone for prophylaxis). Patients who have been diagnosed with SBP will need to continue prophylaxis indefinitely, Dr. Young said.

If you think a patient needs therapeutic paracentesis because of large fluid volume, remember that nature abhors a vacuum, Dr. Young told attendees. "If you pull a lot of fluid out of the belly, they're going to get arterial dilation, they're going to get hypotensive, they get significant untoward events. It's called postparacentesis circulatory dysfunction," he said.

To combat this, give 25 g of 25% albumin for every 5 L of fluid removed, provided kidney function is normal, he noted. In patients with renal insufficiency, use 12.5 g per each 1 to 1.5 L of fluid instead. If the patient has pulmonary hypertension, give the full dose of albumin before the fluid is removed to avoid any potential complications, Dr. Young said.

Upper GI bleeds complicating cirrhosis

According to the speaker infection of some sort is present in 50% of patients, so antibiotics are recommended. The speaker recommended a hemoglobin goal of 8. I am not sure what this means in terms of a transfusion threshold but 7 is now considered evidence based, pretty much across the board.

You can give acetaminophen judiciously.

If you have to give something for pain or fever it's at least better than NSAIDs.

If a stable patient decompensates while in the hospital---

From the article:

"If somebody decompensates, remember GI bleed," Dr. Young said. SBP is also a common cause of decompensation, he noted. "If you tapped them when they came in and they didn't have [SBP], and they remain in the hospital for a little while, and all of a sudden they're just not doing well for reasons you can't entirely explain, don't forget to go back and perform a paracentesis there," he said. If the patient didn't get imaging, it's important to look for hepatocellular carcinoma, a not uncommon cause of decompensation, he noted.

Rethinking the value of the hospitalist model

Here's an interesting study in the Journal of General Internal Medicine looking at the effect of availability of hospitalists on the productivity of primary care physicians (PCPs). From the paper:

KEY RESULTS

We found that the use of hospitalists was significantly associated with a decreased number of hospital visits. The use of hospitalists was also associated with an increased number of office visits, but this was only significant for high users. Physicians who used hospitalists for more than three-quarters of their hospitalized patients had an extra 8.8 office visits per week on average (p = 0.05), which was equivalent to a 10 % increase in productivity over the predicted mean of 87 visits for physicians who did not use hospitalists. We did not find any significant differences in direct patient care time per visit.

CONCLUSIONS

Our study demonstrates that the increase in productivity for the one-third of PCPs who use hospitalists extensively may not be sufficient to offset the current loss of PCP workforce. However, our findings provide cautious optimism that if more PCPs effectively and efficiently used hospitalists, this could help mitigate a PCP shortage and improve access to primary care services.

This effect was more modest than I would have expected. An accompanying editorial estimates that only about one third of PCPs turn 75% or more of their inpatients over to hospitalists. That surprises me but if true means that penetration by hospitalists is far from complete, the niche will continue to expand, and the shortage of hospitalists will continue. The editorial is available as free full text here.

What interests me even more about the editorial is that the author, himself an academic hospitalist, gives a surprisingly objective assessment of the hospitalist model. For years hospitalist leaders have promoted the field with unsubstantiated claims and wishful thinking. These promotions range form statements that hospitalists increase the efficiency of resource utilization to more grandiose ideas about hospitalists being the grand integrators of health care. They have masterfully succeeded in turning this into a popular narrative despite a lack of evidence.

Dr. David Meltzer, the author of the editorial, acknowledges the lack of evidence. From the editorial:

However, there are still no randomized controlled trials (RCTs) that compare the outcomes of care by hospitalists to care by PCPs who care for their own patents in the inpatient and outpatient setting.

Meltzer goes further to say that the old model may even be better:

At one level, the absence of rigorous RCT data comparing the hospitalist model and the traditional model is unfortunate, as these data could inform a range of clinical and policy decisions. However, if the analysis by myself and Chung, as supported by the findings of Park and Jones, is correct, then the decline of PCPs that see patients both in clinic and the hospital may be a largely inevitable result of the time costs of trying to work in both settings, especially as ambulatory volumes increase relative to hospital volumes, so that a daily trip to the hospital has declining economic and clinical benefits relative to costs. Given the rich evidence to support the value of continuity in the doctor–patient relationship,6 – 9 it is plausible that patient benefits or health system savings would be large enough to overcome this economic pressure but it seems unlikely we will ever know this for certain.

Research comparing the hospitalist model with traditional care is beset with low level methodology, mixed results and publication bias. (The publication bias is illustrated by failure to publish this disappointing study, tossed down the memory hole after being presented at the SHM 2005 national meeting).

The piece concludes by suggesting another model:

One model that we have been examining is what we call the Comprehensive Care Physician (CCP) model.10 In this model, patients at increased risk of hospitalization receive care from the same physician in the inpatient and outpatient setting. The CCPs are able to care for these patients in both settings, because they focus their practice on a small panel of less than 200 patients at high risk of hospitalization, so that their clinic volumes are low enough that they can spend each morning seeing their own patients in the hospital, while the acuity of their panel is high enough that they consistently have enough hospitalized patients to justify their daily presence there even with their small panel size. We are currently evaluating the CCP model at the University of Chicago through a randomized trial funded by the Center for Medicare and Medicaid Innovation, with results expected within 2 years.

Those CCPs were the internists of a few decades ago. It's pretty much the old traditional model. The results, if favorable, could drive policy back in that direction. But in order to convince clinic internists to return to the hospital the system would have to provide them professional rewards and pay them handsomely. Given the emerging trends toward compensation for artificial performance metrics that seems unlikely to happen anytime soon.

Systematic review of fecal transplant for C diff

Only two RCTs and some lower level data were available in this review in the Annals of Internal Medicine. From the review:

Study Selection: Any study of FMT to treat adult patients with CDI; case reports were only used to report harms.

Data Extraction: Data were extracted by 1 author and verified by another; 2 authors independently assessed risk of bias and strength of evidence.

Data Synthesis: Two randomized, controlled trials (RCTs); 28 case-series studies; and 5 case reports were included. Two RCTs and 21 case-series studies (516 patients receiving FMT) reported using FMT for patients with recurrent CDI. A high proportion of treated patients had symptom resolution; however, the role of previous antimicrobials is unclear. One RCT comparing FMT with 2 control groups (n = 43) reported resolution of symptoms in 81%, 31%, and 23% of the FMT, vancomycin, or vancomycin-plus-bowel lavage groups, respectively (P less than 0.001 for both control groups vs. FMT). An RCT comparing FMT route (n = 20) reported no difference between groups (60% in the nasogastric tube group and 80% in the colonoscopy group; P = 0.63). Across all studies for recurrent CDI, symptom resolution was seen in 85% of cases. In 7 case-series studies of patients with refractory CDI, symptom resolution ranged from 0% to 100%. Among 7 patients treated with FMT for initial CDI, results were mixed.

Limitation: Most studies were uncontrolled case-series studies; only 2 RCTs were available for analysis.

Conclusion: Fecal microbiota transplantation may have a substantial effect with few short-term adverse events for recurrent CDI. Evidence is insufficient on FMT for refractory or initial CDI treatment and on whether effects vary by donor, preparation, or delivery method.

Folic acid for primary stroke prevention

From the CSPPT RCT:

Design, Setting, and Participants The China Stroke Primary Prevention Trial, a randomized, double-blind clinical trial conducted from May 19, 2008, to August 24, 2013, in 32 communities in Jiangsu and Anhui provinces in China. A total of 20 702 adults with hypertension without history of stroke or myocardial infarction (MI) participated in the study.

Interventions Eligible participants, stratified by MTHFR C677T genotypes (CC, CT, and TT), were randomly assigned to receive double-blind daily treatment with a single-pill combination containing enalapril, 10 mg, and folic acid, 0.8 mg (n = 10 348) or a tablet containing enalapril, 10 mg, alone (n = 10 354)...

Results During a median treatment duration of 4.5 years, compared with the enalapril alone group, the enalapril–folic acid group had a significant risk reduction in first stroke (2.7% of participants in the enalapril–folic acid group vs 3.4% in the enalapril alone group; hazard ratio [HR], 0.79; 95% CI, 0.68-0.93), first ischemic stroke (2.2% with enalapril–folic acid vs 2.8% with enalapril alone; HR, 0.76; 95% CI, 0.64-0.91), and composite cardiovascular events consisting of cardiovascular death, MI, and stroke (3.1% with enalapril–folic acid vs 3.9% with enalapril alone; HR, 0.80; 95% CI, 0.69-0.92). The risks of hemorrhagic stroke (HR, 0.93; 95% CI, 0.65-1.34), MI (HR, 1.04; 95% CI, 0.60-1.82), and all-cause deaths (HR, 0.94; 95% CI, 0.81-1.10) did not differ significantly between the 2 treatment groups. There were no significant differences between the 2 treatment groups in the frequencies of adverse events.

Conclusions and Relevance Among adults with hypertension in China without a history of stroke or MI, the combined use of enalapril and folic acid, compared with enalapril alone, significantly reduced the risk of first stroke. These findings are consistent with benefits from folate use among adults with hypertension and low baseline folate levels.

Ketoacidosis related to sodium-glucose cotransporter-2 (SGLT-2) inhibitors inhibitors in treatment of type 2 diabetes

As reported in Pharmacy Times, according to a new FDA warning 20 post marketing cases have been cited. Some were ketosis without full blown ketoacidosis. Current drugs in this new class are canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance).

How might these drugs cause ketoacidosis? No mechanism was cited in this report. I can speculate on a few. Because they cause glycosuria, there are a number of consequences that might tip a patient over who has marginal insulin reserve (including patients thought to have type 2 diabetes but who actually have some atypical form). First, glycosuria dumps calories which could cause a catabolic state. In association with this already marginal insulin levels might fall. If the glycosuria results in volume depletion the neurohumoral response is counter regulatory and antagonistic to insulin. Finally, the agents increase the risk for urinary tract infections which might lead to decompensation.

Coronary fractional flow reserve

Here is a recent free full textreview.

Revised TPA contraindications in acute ischemic stroke

The labeling changes are summarized here in a post from Emergency Medicine PharmD.

In general the contraindications have eased and there are now vague statements open to wider ranges of interpretation.

Specifically:

“Evidence of intracranial hemorrhage on pretreatment evaluation” has been replaced with “Current intracranial hemorrhage.” The new wording here apparently means the FDA intends a change but it's a mystery to me what the change actually is.

“Suspicion of subarachnoid hemorrhage” has been replaced with “Subarachnoid hemorrhage,” thus ignoring the slight possibility that a patient with a sudden severe headache could have SAH despite a negative CT. Has the FDA decided this is a chance worth taking? After all, no one is going to do an LP before treating with TPA.

Prior stroke (implied in the old labeling to have been within three months) has been eliminated from the contraindications.

“Intracranial neoplasm, arteriovenous malformation, or aneurysm” is replaced with “Presence of intracranial conditions that may increase the risk of bleeding (e.g., some neoplasms, arteriovenous malformations, or aneurysms),” implying that there may be other intracranial contraindicating conditions and some neoplasms that are not contraindications.

A list of specific coagulopathies and contraindicating antithrombotic drugs has been replaced by the term “Bleeding diathesis.”

The specific blood pressure contraindication has been replaced by the general statement “Current severe uncontrolled hypertension.”

Seizure at presentation and history of intracranial hemorrhage have been eliminated from the contraindications.

Treatment of iron deficiency with oral supplements

A nice overview at ClinicalCorrelations.

Extra-intestinal C diff

From a Mayo Clinic Proceedings review:

Overall, 40 patients with extraintestinal CDI were identified: 25 had abdominopelvic infections, 11 had bloodstream infections, 3 had wound infections, and 1 had pulmonary infection. C difficile was isolated with other organisms in 63% of cases. A total of 85% of infections were nosocomial. Factors associated with extraintestinal CDI included surgical manipulation of the gastrointestinal tract (88%), recent antibiotic exposure (88%), malignant tumors (50%), and proton pump inhibitor use (50%). Diarrhea was present in 18 patients (45%), 12 of whom had C difficile polymerase chain reaction (PCR)–positive stool samples. All isolates tested were susceptible to metronidazole and piperacillin-tazobactam. Management included both antimicrobial therapy and guided drainage or surgical intervention in all but one patient. The infection-associated mortality rate was 25%, with death a median of 16 days (range, 1-61 days) after isolation of C difficile.

Drug induced thrombotic microangiopathy

From a systematic review in Blood:

Seventy-eight drugs were described; 22 had evidence supporting a definite causal association with TMA. Three drugs accounted for 61 of the 104 patient reports with definite evidence (quinine, 34; cyclosporine, 15; tacrolimus, 12). Twenty additional drugs had evidence supporting a probable association with TMA.

Via Hospital Medicine VirtualJournal Club.

A systematic review of reperfusion strategies for stroke

From JAMA:

Evidence Review Systematic literature search of MEDLINE databases published between January 1, 1990, and February 11, 2015, was performed to identify studies addressing the role of thrombolysis and mechanical thrombectomy in acute stroke management. Studies included randomized clinical trials, observational studies, guideline statements, and review articles. Sixty-eight articles (N = 108 082 patients) were selected for review.

Findings Intravenous thrombolysis is the mainstay of acute ischemic stroke management for any patient with disabling deficits presenting within 4.5 hours from symptom onset. Randomized trials have demonstrated that more patients return to having good function (defined by being independent and having slight disability or less) when treated within 4.5 hours after symptom onset with intravenous recombinant tissue plasminogen activator (IV rtPA) therapy. Mechanical thrombectomy in select patients with acute ischemic stroke and proximal artery occlusions has demonstrated substantial rates of partial or complete arterial recanalization and improved outcomes compared with IV rtPA or best medical treatment alone in multiple randomized clinical trials. Regardless of mode of reperfusion, earlier reperfusion is associated with better clinical outcomes.

Conclusions and Relevance Intravenous rtPA remains the standard of care for patients with moderate to severe neurological deficits who present within 4.5 hours of symptom onset. Outcomes for some patients with acute ischemic stroke and moderate to severe neurological deficits due to proximal artery occlusion are improved with endovascular reperfusion therapy.

I wonder how the TPA cynics will knock this one down.

New guidelines from ACCP on prevention of COPD exacerbations

Free full text here.

Don't forget constrictive pericarditis

A curable diastolic heart failure.

Via Hospital Medicine VirtualJournal Club.