Management of patients hospitalized with asthma exacerbation

This post draws from a talk given by Prescott Woodruff, MD, MPH at UCSF's 17th annual hospital medicine conference.


Asthma subtypes

There are numerous classifications of asthma and they overlap somewhat. A useful one for the hospital presentation of asthma is type 1 versus type 2. Type 1 is by far the most common and is mediated by inflammatory cell infiltration and mucus plugging. As such it is gradual in onset and slow to resolve. Type 2, sometimes referred to as “sudden asphyxic asthma,” has a more rapid onset but also responds more rapidly to treatment. It is characterized by intense bronchospasm and less of an inflammatory component. Review here.


Corticosteroids: Dose? Route?

High level evidence to guide clinicians is lacking. The “official” recommendation is to start with oral and switch to IV if poor response. The speaker initiates IV therapy in critically ill patients.


Levalbuterol versus albuterol

Evidence mixed, controversy unresolved. It may not matter.


Antibiotics?

Not generally recommended for asthma per se but indicated if specific signs/sx of infection e.g. fever, purulency. Don't forget sinusitis.


Theophylline

Forget about it.


Ipratropium

Probably helpful as an adjunct.


Heliox

No evidence that it impacts hard clinical outcomes but works fast and may buy time initially until other therapies take effect. [1] [2] If FiO2 of over 40% is required it's not a good option (you can't mix in enough helium).


IV magnesium

2 grams IV may help as an adjunct to improve pulmonary function during the initial management of severe attacks.

Destructive games involving doctors and patients

I found particularly interesting in this review the list of destructive games played between doctors and patients:

Wooden leg Possessing a disability as a justification for choices or behavior which in the average person may be considered unacceptable.

Why don't you… Yes, but  The player reports a problem despite having been presented with solutions to it, to gain confirmation that his/her issue is “insoluble.”

Now I've got you If one party of a usually not-clearly-defined contract even slightly exceeds its boundaries, the other party, the player, thinks he/she is permitted to react in a forceful way, possibly with full rage.

How do you get out of here? In case of failure of repeated mock efforts the player can avoid a possible consequence of achieving success and feel “justified” in this situation.

Clinic Because both parties of a contract benefit from it they do not want to give it up, even if there is really no need to continue it.

The doctor can be a passive or active participant in the games. Elaboration is found in the body of the paper which is free full text.

Mortality and choice of oral hypoglycemic

Metformin wins, sulfonylureas lose. From a recent study:

Methods

We identified new users of oral hypoglycaemic medication monotherapy between 2004 and 2009 who received care for at least 1 year from the Veterans Health Administration. Patients were followed until initial monotherapy discontinuation, addition of another diabetes pharmacotherapy, death or end of follow-up. Mortality HRs were estimated using Cox regression adjusted for potential confounding factors.

Results

Among new users of metformin, sulfonylureas and rosiglitazone (185,360 men, 7,812 women), 4,256 (2.2%) died during follow-up. Average duration of medication use ranged from 1.4 to 1.7 years. Significantly higher mortality risk was seen for glibenclamide (known as glyburide in the USA and Canada) (HR 1.38, 95% CI 1.27, 1.50) or glipizide (HR 1.55, 95% CI 1.43, 1.67) compared with metformin monotherapy, and for glipizide compared with rosiglitazone (HR 1.27, 95% CI 1.01, 1.59) or glibenclamide monotherapy (HR 1.12, 95% CI 1.02, 1.23). A significant sex–rosiglitazone interaction was seen (p = 0.034) compared with metformin monotherapy, with women having a higher HR (HR 4.36, 95% CI 1.34, 14.20) than men (HR 1.19, 95% CI 0.95, 1.49).

Conclusions/interpretations

Significantly higher mortality was associated with glibenclamide, glipizide and rosiglitazone use compared with metformin, and with glipizide use compared with rosiglitazone or glibenclamide. The potential for residual confounding by indication should be considered in interpreting these results.

The Berlin definitions for ARDS

Here is a recent review.

The new classification removes the category formerly known as ALI. The definition also removes the quantitative assessment for cardiogenic pulmonary edema, thus relying on clinical circumstances and assessment. The addition of minimum PEEP levels to satisfy the definition would exclude non intubated ward patients who were included under the old definition.

Takotsubo cardiomyopathy due to inhaled beta agonists

Takotsubo cardiomyopathy (TC), in our current understanding, is a disorder of catecholamine myocardial toxicity. Early descriptions attributed it to endogenous catecholamine excess triggered by emotional stress. Over time physical stressors, especially acute illnesses, were recognized as triggers. Exogenous catecholamines as triggers are supported by animal data and have been only occasionally reported clinically.

Here [1] [2] are two reports of TC complicating acute exacerbations of asthma and COPD, triggered by inhaled beta agonists. Arrhythmia and hypokalemia are additional complications of beta agonists. This alongside the considerable overlap between COPD and CAD highlights the importance of cardiac precautions in appropriate patients.

Venous thromboembolism in cancer patients

Though there is a relative lack of high level evidence regarding this condition we do know that it differs in important ways from VTE in the general population. Below are some key points from a recent review.


Initial treatment

Acceptable alternatives include low molecular weight heparin (LMWH), unfractionated heparin (UFH), and fondaparinux. LMWH seems to be associated with a mortality benefit and is favored over the other two.


Thrombolysis

Little evidence exists to guide clinicians. Though special vigilance is needed to exclude patients with cancer associated bleeding risks (eg CNS involvement) patient selection in general is similar to that in the general population.


Continued management after the first few days

Here is where we have the best evidence. Several open label RCTs and a meta-analysis favor LMWH over warfarin for the next 3 to 6 months at least if the patient has normal renal function.


Duration of treatment

Cancer patients have an increased risk of recurrent VTE on and off treatment. They also have an increased risk of anticoagulant related bleeding in many circumstances. The review states that extended anticoagulation (beyond 3-6 months) “be considered” in this population. So just as with the ACCP guideline recommendation on this question for the general VTE population, considerable wiggle room is given for clinician judgment and patient preference.


IVC filters

IVC filters are thrombogenic and even more so in cancer patients. The review authors recommend against IVC placement unless there is an acute VTE with contraindication to anticoagulation, which is consistent with the more conservative of the various guidelines for the general population.


Management of recurrent VTE while on treatment

True anticoagulant failure is believed to be rare in the general population but according to the review is common in the setting of cancer. Strategies to deal with this situation involve first ruling out HIT, non compliance or subtherapeutic anticoagulation. In the event of true anticoagulant failure increasing the intensity of anticoagulation is recommended, either by switching to a superior anticoagulant or increasing the dose of the existing anticoagulant. An algorithm is presented in the review.


Novel oral anticoagulants

The authors recommend against the use of these agents in cancer associated VTE until more research evidence is available.

Approach to the hospitalized patient with altered mental status

These are a few pearls from a talk by S. Andrew Josephson MD at UCSF's 17th annual hospital medicine conference.


Dementia with Lewy bodies (DLB)

Associated with parkinsonism.

Visual hallucinations.

Has a fluctuating course so may present as delirium.

Antipsychotics contraindicated. Cholinergics help.

Here are some links [1] [2]


HSV-1 meningoencephalitis

Tests may be negative initially. Speaker's comment: “We start a lot of confused patients on acyclovir.” (IV).


Wernike's

Triad: confusion, ataxia, occulomotor.

Alcoholism no longer the leading risk factor!

Low threshold to give IV thiamine in confused patient.


Agitated delirium

Non pharmacologic modalities are the treatment of choice. Drugs as a last resort (exception: ETOH withdrawal).

Benzos make it worse (exception: ETOH).

Antipsychotics may be necessary but contraindicated in some patients (e.g. Lewy body).

The peri go-live period and patient safety risk

It's something people don't want to talk about. For that matter neither do I, so just go and read this.

Noninvasive ventilation for acute severe asthma: is it appropriate?

There are limited data, summarized in a recent review:

Purpose of review

The use of noninvasive positive pressure ventilation (NPPV) is often employed for the management of acute respiratory failure as an alternative to endotracheal intubation and mechanical ventilation. However, evidence to support the application of NPPV use in patients with acute severe asthma is less known.

Recent findings

A paucity of evidence is available to support the use of NPPV as part of clinical care in patients with acute severe asthma. A number of small studies in adult and paediatric populations suggest that NPPV may have a beneficial role through improving respiratory rate and reducing the need for more invasive alternatives. Overall NPPV use appeared to be well tolerated with few reports of adverse events.

Hantavirus twenty years later

We've learned a great deal since the outbreak in the Four Corners region in 1993. Full text here.

Drug culprits in ANCA associated vasculitis

It is increasingly appreciated that a positive ANCA and various associated clinical manifestations can be associated with certain drugs. From a recent review:

Hydralazine, minocycline, propylthiouracil and levamisole-adulterated cocaine use should be closely considered in any patient where ANCA vasculitis is entertained given the wide use of these drugs in the community. Furthermore, medical practitioners should test urine for the presence of cocaine in any patient with presumed ANCA vasculitis, and if positive, then urine should also be tested for levamisole. Clinical features can be severe requiring not only drug cessation and supportive care, but also immunosuppression, plasma exchange in severe cases and dialysis as needed. Clinical trial investigators should strongly consider excluding patients with drug-induced forms of disease and mechanistic inroads are greatly needed in these secondary forms of disease to help elucidate the underlying cause and pathogenesis of ANCA vasculitis.

Drug induced channelopathies

Long QT, Brugada syndrome and short QT can be induced by drugs and the topic is covered in this review. Both cardiac and non cardiac drugs are on the list. Long QT inducing drugs are primarily potassium channel blockers but there are other mechanisms. Brugada pattern inducing drugs are sodium channel blockers and include class 1 antiarrhythmics, TCAs and other psychiatric drugs. The list of drugs inducing short QT is short but likely to expand. Many of the short QT inducing drugs were discovered and removed in preclinical development. Patients who experience drug induced channelopathies may be genetically susceptible and have a forme fruste of the condition. The paper, which is available as free full text at the link above, contains links to web resources for drugs to avoid as well as other precautions in syndromic patients.

Chemistry videos

An assortment of videos generated automatically by You Tube's video discovery system.

Takayasu arteritis

Here's a Mayo Clinic series. The disease is rare. Diagnostic delay is characteristic because when the disease is encountered it tends to be attributed to the ordinary atherosclerotic process. The patients tend to have the traditional risk factors. Think of it in those youngish patients who present as “vasculopaths.”  

Incidentally discovered pulmonary nodules

Hospitalists encounter this situation all the time when chest CTs are done for other reasons. A nice summary post at ERCAST addresses the topic. The emergency physician's perspective on this is pretty much the same as the hospitalist's. Informing the patient and documenting it in the medical record (including stating in the record what the patient was told) is our responsibility, not long term follow up and definitive evaluation. The post has some tips and scripts for how to have the conversation, some pearls about pulmonary nodules and a link to the Fleischner Society recommendations.

Propofol infusion syndrome (PRIS)

This is actually a case report of PRIS treated with ECMO but attached is a nice mini-review of the condition.

The pathophysiology is complex but apparently involves, among many other things, impaired ability of FFA to enter the mitochondria for oxidation (as in Reye's syndrome or carnitine deficiency?) and impaired electron transport.

The association of inflammatory myopathy with underlying malignancy

Understanding of this association has increased in recent years. Here is an update, which contains several pearls. Free full text.  

Extended infusion cefepime

As compared to conventional dosing it appears to be associated with a marked reduction in mortality in Pseudomonas aeruginosa infections:

We evaluated the clinical and economic outcomes associated with extended-infusion cefepime in the treatment of P. aeruginosa infections. This single-center study compared inpatients who received cefepime for bacteremia and/or pneumonia admitted from 1 January 2008 through 30 June 2010 (a 30-min infusion of 2 g every 8 h) to those admitted from 1 July 2010 through 31 May 2011 (a 4-h infusion of 2 g every 8 h). The overall mortality was significantly lower in the group that received extended-infusion treatment (20% versus 3%; P = 0.03). The mean length of stay was 3.5 days less for patients who received extended infusion (P = 0.36), and for patients admitted to the intensive care unit the mean length of stay was significantly less in the extended-infusion group (18.5 days versus 8 days; P = 0.04). Hospital costs were $23,183 less per patient, favoring the extended-infusion treatment group (P = 0.13). We conclude that extended-infusion treatment with cefepime provides increased clinical and economic benefits in the treatment of invasive P. aeruginosa infections.

Over the last few years a number of publications [1] [2] [3] raised safety concerns regarding cefepime, noting a poorly understood association with increased mortality. Neurotoxicity was cited as a possible mechanism. Extended-infusion dosing might mitigate toxicity by means of lower maximum blood levels.

Via Hospital Medicine Virtual Journal Club.

Capnography

Learn all about it. Lots of resources here.

JNC 8: the minority opinion

Several members of the panel disagreed with portions of the JNC 8 guidelines and expressed their concerns in this article in the Annals of Internal Medicine. It is available as free full text. From the introduction:

The “2014 Evidence-Based Guideline for the Management of High Blood Pressure In Adults: Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8)” recommends several major changes from the JNC 7 report (1–2). The 2014 guideline is based on a systematic review of randomized, controlled trials (RCTs) by a multidisciplinary panel using a process informed by Institute of Medicine recommendations for guideline development (3). Although there was almost unanimous agreement on nearly all recommendations, a minority of the panel (the authors of this commentary) disagreed with the recommendation to increase the target systolic blood pressure (SBP) from 140 to 150 mm Hg in persons aged 60 years or older without diabetes mellitus (DM) or chronic kidney disease (CKD). This target guides both the initiation of therapy and treatment goals. Although this issue has major clinical and public health implications, the guideline only briefly summarized the concerns underlying the minority opinion to maintain the target of less than 140 mm Hg. The Institute of Medicine recommendation for guideline development encourages guidelines to provide “a description and explanation of any differences of opinion regarding the recommendation” (3). This article summarizes the evidence and rationale underlying the minority opinion to maintain the SBP target of 140 mm Hg or lower in persons aged 60 years or older until there is greater certainty of the risks and benefits of a higher target.

The authors make a strong case. The more clinical trials published on a topic the more ways there are to combine and interpret the findings. And in hypertension the number of trials is very large. It rivals all of medicine in the number of trials published. There will be much more discussion about this. Guidelines from ACC/AHA are due out soon I'm told.

More from Medpage Today.