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(Chest. 2003;124:1880-1884.)
© 2003 American College of Chest Physicians

Profile of Near-Fatal Asthma in an Inner-City Hospital*

Sunil Dhuper, MD, FCCP; Diane Maggiore, MD; Virginia Chung, MD and Chang Shim, MD, FCCP

* From Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY.

Correspondence to: Sunil Dhuper, MD, FCCP, Department of Medicine, North Central Bronx Hospital, 3424 Kossuth Ave, Bronx, NY 10467; e-mail: dhupernbhn{at}aol.com


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Study objectives: Patients requiring mechanical ventilation for asthma are at a high risk of similar attacks and death in the future. Early recognition and treatment with systemic corticosteroids (SC) can influence outcome in near-fatal asthma (NFA). We studied the ability of patients to recognize the severity of asthma, implement SC therapy, and seek timely help from a health-care provider (HCP).

Design: Retrospective review of patient histories and medical records.

Setting: Medical ICU and inpatient medical ward of an inner-city university hospital.

Patients: Asthma patients requiring mechanical ventilation.

Methods: Seventy episodes of NFA requiring endotracheal intubation (intubation group [IG]) and 523 hospital admissions with acute asthma (nonintubation group [NIG]) were analyzed over a 4-year period from January 1997 to September 2000. Prior intubation(s), duration of symptoms, steroid dependence, and knowledge and use of inhaled corticosteroids and SC were noted. Indications for mechanical ventilation, ventilatory parameters using permissive hypercapnia, sedation/paralysis, duration, extubation criteria, complications, and outcome were analyzed.

Results: Twenty-nine of 70 patients (41.4%) in the IG had at least one prior episode of NFA requiring mechanical ventilation, compared to 123 of 523 patients (23.5%) in the NIG (p < 0.005). Ten of 70 patients (14.3%) in the IG were steroid dependent, compared to 40 of 523 patients (7.6%) in the NIG (p < 0.05). Forty of 70 patients (57%) in the IG compared to 308 of 523 patients (59%) in the NIG reported noncompliance with prescribed inhaled corticosteroids (not significant). All received aerosolized ß-agonist therapy, but only 11 of 70 patients (15.7%) initiated SC therapy in the IG compared to 145 of 523 patients (27.7%) in the NIG (p < 0.05). Even with symptoms > 48 h, 34 of 43 patients (79%) in the IG did not receive SC. Three patients died and four patients acquired myopathy in the IG.

Conclusion: History of intubation and steroid dependence were identified as risk factors for future intubation. Our patients with asthma in both the IG and NIG were noncompliant with inhaled corticosteroids. Despite a long duration of symptoms and knowledge of SC, the majority neither implemented self-management with SC nor contacted an HCP. Early initiation of SC (symptoms < 48 h) might have averted intubation in the high-risk group. Most of our patients were extubated successfully in < 48 h. Incidence of barotrauma was very low, probably due to utilization of permissive hypercapnia.

Key Words: corticosteroids • mechanical ventilation • near-fatal asthma


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Asthma is a serious and growing health-care concern.1 The prevalence and severity of asthma, as well as its associated morbidity and mortality, have increased in the last few decades.2 3 In the United States, 40 million people have asthma. They account for 3 million emergency department (ED) visits, 500,000 hospitalizations, and nearly 6,000 deaths annually. Our institution (Jacobi Medical Center, Bronx, NY) serves a population with a high prevalence of asthma, and has a long history of interest in the management of acute and chronic asthma. In this study, we reviewed approximately 4 years of our experience with asthma patients, and compared the profile of patients who required mechanical ventilation with those hospitalized for acute asthma but not requiring mechanical ventilation.

Mechanical ventilation for asthma is a relatively rare occurrence; however, asthma patients who require mechanical ventilation have a high morbidity and mortality. Patients with a severe asthma attack who have survived an episode of endotracheal intubation and mechanical ventilation for acute respiratory failure are designated to have experienced near-fatal asthma (NFA). Several studies4 5 6 revealed that such patients are at increased risk of a similar severe attack and, hence, death in the future. As early recognition of a severe attack and treatment with systemic corticosteroids (SC) is essential to improve outcome for NFA, we analyzed our patients’ knowledge and practices prior to presentation.

The aims of this study were to evaluate patients presenting with NFA for the following: their ability to recognize the increasing severity of the asthma exacerbation; their ability to seek timely help from a health-care provider (HCP); their knowledge of corticosteroid use, inhaled and systemic; their implementation of such therapy; and their hospital course, especially mechanical ventilation and outcomes.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
We evaluated 70 episodes of NFA requiring endotracheal intubation and mechanical ventilation, and compared these profiles to 523 patients hospitalized for acute asthma from January 1997 to September 2000. Patient histories and medical records were retrospectively reviewed as part of an ongoing quality improvement project for asthma care. Only those patients who met the criteria for asthma set forth by the American Thoracic Society7 were included in the study, and any patients with evidence of chronic bronchitis and emphysema were excluded. Data detailing the characteristics of all asthmatics requiring intubation and mechanical ventilation were collected from the time of the patient’s first contact with the HCP until the patient was discharged from the hospital.

All patients were initially evaluated in the ED and admitted to either the medical ICU or the medical floor. Indications for hospitalization were based on the guidelines defined by National Asthma Education and Prevention Program.8 Although indications for mechanical ventilation in acute asthma exist, many of these guidelines are arbitrary. Indications for intubation and mechanical ventilation in our study fell into two categories: immediate intubation and delayed intubation. A decision was made to administer mechanical ventilation immediately in the event of cardiopulmonary arrest, loss of consciousness, and/or altered mental status. Patients in the delayed category were treated with humidified oxygen, nebulized albuterol, 2.5 mg every 15 min three times and then every 1 h; epinephrine, 1:1000 concentration, 0.3 mL subcutaneously every 15 min three times in some cases; and high dose IV steroids in all cases. Mechanical ventilation was instituted if patients demonstrated deteriorating gas exchange and respiratory failure documented by arterial blood gas or if clinical parameters suggested impending respiratory failure (indicated by tachycardia, worsening respiratory distress with use of accessory muscles, exhaustion or fatigue in the judgment of physician or patient, and deteriorating peak expiratory flow rates).

Patients received controlled mechanical ventilation utilizing the principles of permissive hypercapnia. The ventilator settings were adjusted to maintain peak airway pressure < 50 cm H2O, irrespective of the PCO2 level. Sedation was maintained with benzodiazepines or propofol, either IV push or continuous infusion. Neuromuscular blocking agents were used sparingly and only if the above measures failed to achieve the target peak pressure. The inspiratory to expiratory ratio was usually maintained between 1:3 and 1:4. The fraction of inspired oxygen was adjusted to maintain a PaO2 > 60 mm Hg. Patients were maintained on mechanical ventilation until peak airway pressures decreased to <= 35 cm H2O for at least 2 h off sedation and then extubated.

Patients with asthma exacerbation who did not require intubation (nonintubation group [IG]) received similar treatment with humidified oxygen; nebulized albuterol, 2.5 mg every 15 min three times, and then every 4 to 6 h; and IV corticosteroids based on our standard asthma treatment regimen.

Data Collection
We conducted interviews of all patients based on a questionnaire developed by the pulmonary service. We elicited detailed history of the patient’s asthma, current episode of asthma, previous hospitalizations, circumstances leading to the previous hospitalizations, and episodes of NFA. For current episode, the patient was asked to identify the precipitating event, if known, to quantify the duration of symptoms prior to presentation to the emergency department, to list of medications they are prescribed and their actual use of any, and to describe their use of corticosteroids, both aerosol and oral forms in the past and in the 1 month preceding the current admission. They were asked to describe their pattern of health-care utilization; to note whether they had previously received information about asthma and its treatment, specifically the prior instruction on the use of oral corticosteroids during acute asthma attack; and to note whether they were prescribed a spacer and a peak flowmeter. For those who required mechanical ventilation, we scrutinized the records of the ED and the emergency medical service (EMS) to find the indications for mechanical ventilation, ventilatory parameters, and use of sedation and paralytics. The chart was further reviewed to obtain the trend in the ventilatory parameters, use of sedatives and paralytics, extubation criteria, complications, and outcome.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Between January 1997 and September 2000, 70 episodes of asthma in 22 men and 48 women aged 18 to 80 years who required mechanical ventilation were evaluated. Most of the patients were intubated either by EMS in the field (20 of 70 patients) or by a physician in the ED (47 of 70 patients). Two patients were intubated in the medical ICU, and one patient admitted to the medical floor was later intubated and transferred to the medical ICU. During the same time period, there were 523 admissions for acute asthma to the medical floor, 378 women and 145 men aged 18 to 90 years. History of intubation and steroid dependence were the only risk factors identified where a statistically significant difference was found between the IG and the NIG.

Multiple episodes of NFA were not uncommon. Of the 70 episodes of endotracheal intubation, 29 episodes (41.4%) were among patients with at least one prior episode of NFA. Thirteen of these episodes (18.5%) were in patients with a history of three or more previous intubations. Compared to the IG, 123 of 523 patients (23.5%) in the NIG had at least one prior episode of NFA (p < 0.005). Indications for endotracheal intubation included 17 episodes (24%) for altered mental status and 28 episodes (40%) of deteriorating gas exchange on arterial blood gas analysis. Intubation was required for impending respiratory failure in the judgment of the ED attending physician/EMS in the remaining 25 episodes (36%). Ten of 70 patients (14.3%) were steroid dependent in the IG, compared to 40 of 523 patients (7.6%) in the NIG (p < 0.05).

The knowledge and practices of our study group as to treatment strategy prior to presentation, especially corticosteroid use, are outlined in Table 1 . Only 7 of 70 patients (10%) with NFA contacted an HCP, compared to 105 of 523 patients (20%) in the NIG (not significant [NS]). The majority self-managed their asthma exacerbation in both groups. All patients reported using ß-agonist therapy either via metered-dose inhaler and/or nebulizer. Only 30 of 70 patients (43%) in the IG and 215 of 523 patients (41%) in the NIG reported to have received at least 50% of the prescribed inhaled steroid dose in the preceding month. Among the total study population, only 11 of 70 patients (15.7%) in the IG initiated oral corticosteroids prior to endotracheal intubation, compared to 145 of 523 patients (27.7%) in the NIG (p < 0.05).


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  		Table 1.. Influence of Medical Knowledge and History on Asthma Practice*

 
We asked our patients whether they had prior instructions on the initiation of SC during acute asthma exacerbation. Thirty-eight of 70 patients (54.3%) in the IG and 310 of 523 patients (59.3%) in the NIG reported prior instruction on the use of oral corticosteroids during acute asthma; however, only 11 of 38 patients (29%) in the IG implemented oral corticosteroids, compared to 145 of 310 patients (47%) in the NIG, resulting in a higher compliance rate in the NIG (p < 0.05). We assessed the impact of duration of asthma symptoms on corticosteroid utilization, since some patients may have deteriorated rapidly and had no time to initiate a course of oral corticosteroids. The majority of patients, 43 of 70 patients (62%) in the IG (Fig 1 ) and 383 of 523 patients (73.2%) in the NIG had asthma symptoms for > 48 h prior to presentation, giving them adequate time to have started the therapy with SC or to contact an HCP.



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  		Figure 1.. Duration of asthma symptoms prior to endotracheal intubation (IG).

 
The majority of patients (76%) were extubated successfully in < 48 h. The complications of NFA in our study group are reported in Table 2 . Of the three patients who died, two patients had a respiratory arrest at home prior to EMS arrival, and one patient had a respiratory arrest in the hospital. One patient who had a respiratory arrest at home prior to EMS arrival sustained anoxic brain injury. One patient had a non-Q-wave myocardial infarction. Four patients acquired myopathy; however, all were successfully extubated and recovered muscle strength over several weeks.


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  		Table 2.. Mortality and Complications

 

   Discussion
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 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
Patients with asthma who require intubation and mechanical ventilation have a high morbidity, intrahospital mortality,9 and subsequent mortality. One study10 reported a mortality rate of 22%. Several other studies11 12 13 14 15 16 17 18 19 20 reported mortality rates varying from 0 to 38%. A 6-year follow-up study2 of 145 patients showed a posthospitalization mortality of 10.2% at 1 year, 14.4% at 3 years, and 22.6% at 6 years. Most deaths were due to recurrent severe asthma attacks. Most of these patients did not have close follow-up and objective assessment of pulmonary functions. Several studies21 22 23 24 evaluated the risk factors for intubation and markers that predict mortality. Asthma deaths have been associated with a number of avoidable factors and deficiencies in personal and medical management that can potentially be remedied.25 26 27

In this study, we focused on the characteristics and practices of our adult patient population with moderate-to-severe asthma presenting with NFA in an effort to better understand the factors affecting early recognition, treatment implementation, and possible prevention. Forty-one percent of patients in our study group had a history of at least one prior intubation, compared to 23% in the NIG, supporting the finding of increased risk of NFA among patients with a previous history of a similar episode.21 22 23 24 As multiple intubations were not uncommon, emphasis on better overall asthma management of these high-risk patients with chronic anti-inflammatory therapy is essential. Steroid dependence was twice as high in the IG compared to the NIG. In one study,28 a significant reduction in the risk of NFA was shown among patients dispensed >= 12 canisters per year of inhaled corticosteroids. In our study group, we found that 60% of the patients were nonadherent to steroid inhaler use, similar to the adherence rate reported in other studies.21 26 These patients tended to have poor routine care without follow-up in any medical setting, and many used multiple EDs as their primary source of asthma care. As we were not able to successfully influence chronic management, we wanted to further examine acute self-management by these patients prior to presentation.

One of the most important aspects in management of patients at risk for NFA is initiation of SC therapy at the onset of asthma symptoms or timely contact with an HCP. It is disturbing that the majority of our patients had neither instituted SC therapy nor contacted an HCP. Their knowledge of self-management with SC was not implemented. Their fear of side effects of SC, underestimation of attack severity, and prior experience with attacks that had ameliorated without SC made them take a "wait and see" attitude. The fear of complications from SC is pervasive among our asthma patients despite our efforts to educate them of the relative safety of short-burst therapy with oral corticosteroids. Weight gain is of concern especially among young female patients.

Even though the above-mentioned aspects of asthma education are very important, the most critical part of asthma education is to train our patients to recognize the warning signs of life-threatening asthma. All of our patients claimed that they would have either started steroids or contacted an HCP if they had recognized the severity of their asthma. Subjective assessment of asthma severity based on the patient’s perception of symptoms can be quite deceptive. Serial measurement of peak expiratory flow rate is an objective assessment widely used for home monitoring of asthma8 ; however, most of the patients in this study did not own a peak flowmeter, and even the few who owned one did not use it. Instead, they relied on their subjective sensation of asthma. It may be more suitable for our patients to rely on the increasing need for a ß-agonist as a trigger to initiate SC therapy. Patients in our clinic are usually instructed to initiate SC therapy when they increase ß-agonist use to seven or more times in a given day. Those who typically have slow progression of asthma over several days are told to initiate SC therapy when they experience nocturnal worsening of asthma, having to wake up once or more, for 2 consecutive nights.

Clearly, we documented an improvement in the outcome of patients receiving mechanical ventilation for acute asthma. In the past, studies11 12 13 14 15 16 17 18 19 20 29 have shown a significant mortality associated with mechanical ventilation for asthma; however, this is not our experience. Most of our patients were extubated successfully in < 48 h, and the overall complication rate especially from barotrauma was very low, probably because of the use of permissive hypercapnia and maintenance of low peak airway pressure. We found our extubation criteria to be safe and reliable. Patients were extubated when the peak airway pressure decreased to <= 35 cm H2O for 2 h and they were fully awake from sedation.

In conclusion, we have shown that the patients in both groups had poor adherence to inhaled corticosteroids. NFA patients were more likely to have experienced prior endotracheal intubations and to be steroid dependent. Patients with NFA are particularly reluctant to use SC despite their favorable experience with SC in the past and they had adequate time to implement SC therapy. Efforts should be made to stress early asthma intervention and to focus on early recognition of warning signs of objective evidence, ie, measurement of serial peak expiratory flow rates and the increasing need for ß-agonists. Furthermore, our patients with moderate-to-severe asthma need to change their perception of short-burst corticosteroid therapy and accept it as a safe modality of self-management. This needs to be stressed in the ED, during hospital admissions, and in primary care clinics. Such an approach may prevent future episodes of NFA.


   Footnotes
 
Abbreviations: ED = emergency department; EMS = emergency medical service; HCP = health-care provider; IG = intubation group; NFA = near-fatal asthma; NIG = nonintubation group; NS = not significant; SC = systemic corticosteroids

This work was performed at Jacobi Medical Center, Bronx, NY.

Received for publication December 28, 2001. Accepted for publication April 4, 2003.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Weiss, KB, Wagener, DK (1990) Changing patterns of asthma mortality: identifying target populations at high risk. JAMA 264,1683-1687[Abstract]
  2. Weiss, KB, Gergen, PJ, Wagener, DK Breathing better or wheezing worse? The changing epidemiology of asthma morbidity and mortality. Annu Rev Public Health 1993;14,491-513[ISI][Medline]
  3. FitzGerald, JM, Macklem, P Fatal asthma. Annu Rev Med 1996;47,161-168[CrossRef][ISI][Medline]
  4. Marquette, CH, Saulnier, F, Leroy, O, et al Long term prognosis of near-fatal asthma: a 6 year follow up study of 145 asthmatic patients who underwent mechanical ventilation for a near-fatal attack of asthma. Am Rev Respir Dis 1992;146,76-81[ISI][Medline]
  5. Molfino, NA, Nannini, LJ, Rebuck, AS, et al The fatality-prone asthmatic patient: follow-up study after near-fatal attacks. Chest 1992;101,621-623[Abstract/Free Full Text]
  6. Ruffin, RE, Latimer, KM, Schembri, DA Longitudinal study of near-fatal asthma. Chest 1991;99,77-83[Abstract/Free Full Text]
  7. American Thoracic Society. Chronic bronchitis, asthma, and pulmonary emphysema. Am Rev Respir Dis 1987;136,224-225
  8. National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program: Expert Panel Report 2; guidelines for the diagnosis and management of asthma. 1997 National Institutes of Health. Bethesda, MD: publication 97-4051A
  9. Tan, WC, Lim, KP, Ng, TP, et al Long-term asthmatic and disease control in near-fatal asthma. Ann Acad Med Singapore 1999;28,384-388[Medline]
  10. Mansel, JK, Stogner, SW, Petrini, MF, et al Mechanical ventilation in patients with acute asthma. Am J Med 1990;89,42-48[CrossRef][ISI][Medline]
  11. Santiago, SM, Jr, Klaustermeyer, WB Mortality in status asthmaticus: a nine year experience in a respiratory intensive care unit. J Asthma Res 1980;2,75-79
  12. Webb, AK, Bilton, AH, Hanson, GC Severe bronchial asthma requiring ventilation: a review of 20 cases and advice on management. Postgrad Med J 1979;55,161-170[CrossRef][ISI][Medline]
  13. Scoggin, CH, Sahn, SA, Petty, TL Status asthmaticus: a nine-year experience. JAMA 1977;238,1158-1162[Abstract]
  14. Petheram, IS, Branthwaite, MA Mechanical ventilation for pulmonary disease: a six year survey. Anaesthesia 1980;35,467-473[Medline]
  15. Picado, C, Montserrat, JM, Roca, J, et al Mechanical ventilation in severe exacerbation of asthma: study of 26 cases with six deaths. Eur J Respir Dis 1983;64,102-107[ISI][Medline]
  16. Halttunen, PK, Luomanmaki, K, Takkunen, O, et al Management of severe bronchial asthma in an intensive care unit. Ann Clin Res 1980;12,109-111[Medline]
  17. Darioli, R, Perret, C Mechanical controlled hypoventilation in status asthmaticus. Am Rev Respir Dis 1984;129,385-387[ISI][Medline]
  18. Luksza, AR, Smith, P, Coakley, J, et al Acute severe asthma treated by mechanical ventilation: 10 years’ experience from a district general hospital. Thorax 1986;41,459-463[Abstract/Free Full Text]
  19. Westerman, DE, Benatar, SR, Potgieter, PD, et al Identification of the high-risk asthmatic patient: experience with 39 patients undergoing ventilation for status asthmaticus. Am J Med 1979;66,565-572[CrossRef][ISI][Medline]
  20. Higgins, B, Greening, AP, Crompton, GK Assisted ventilation in severe acute asthma. Thorax 1986;41,464-467[Abstract/Free Full Text]
  21. Lin, RY, Rehwan, A Clinical characteristics of adult asthmatics requiring intubation. J Med 1995;26,261-277[CrossRef][ISI][Medline]
  22. LeSon, S, Gershwin, ME Risk factors for intubation of adult asthmatic patients. J Asthma 1995;32,97-104[Medline]
  23. LeSon, S, Gershwin, ME Risk factors for asthmatic patients requiring intubation III: observations in young adult patients. J Asthma 1996;33,27-35[ISI][Medline]
  24. Kurohara, ML, Placik, IM, Klanstermeyer, WB Asthma: analysis of intubated patients over a year period. Mil Med 1996;161,567-570[Medline]
  25. Clark, NM, Starr-Schneidkraut, NJ Management of asthma by patients and families. Am J Respir Crit Care Med 1994;149,S54-S66[ISI][Medline]
  26. Rand, CS, Wise, RA Measuring adherence to asthma medication regimens. Am J Respir Crit Care Med 1994;149,S69-S76[ISI][Medline]
  27. Turner, MO, Noertjojo, K, Vedel, S, et al Risk factors for near-fatal asthma: a case-control study in hospitalized patients with asthma. Am J Respir Crit Care Med 1998;157,1804-1809
  28. Ernst, P, Spitzer, WO, Suissa, S, et al Risk of fatal and near-fatal asthma in relation to inhaled corticosteroid use. JAMA 1992;268,3462-3464[Abstract]
  29. Finfer, SR, Garrard, CS Ventilatory support in asthma. Br J Hosp Med 1993;49,357-360[Medline]



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