==== Front Ann Saudi MedAnn Saudi MedAnnals of Saudi Medicine0256-49470975-4466King Faisal Specialist Hospital and Research Centre 1714302310.5144/0256-4947.2006.461asm-6-461Original ArticleOutcome of patients with severe asthma in the intensive care unit Alzeer Abdulaziz BaHammam Ahmed Masood Mohammed Basha Sayed Jani Alhamad Esam Sohail Sayed From the Department of Medicine, King Khalid University Hospital, Riyadh, Saudi ArabiaCorrespondence and reprint requests: Abdulaziz Alzeer, MD, King Khalid University Hospital, Department of Medicine, P.O. Box 18321, Riyadh 11415, Saudi Arabia, T: +966-1-467 1521, F: +966-1-467 9495, alzeerahm@yahoo.comNov-Dec 2006 26 6 461 465 01 10 2006 Copyright © 2006, Annals of Saudi Medicine2006This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.BACKGROUND Because little has been reported about the outcome of severe asthma outside the US and western Europe, we performed a retrospective case analysis of patients treated in the medical intensive care unit (MICU) of a university hospital in Riyadh, Saudi Arabia, to determine the management, complications and outcome of severe asthma requiring ICU admission. METHODS The records of patients with severe asthma admitted to the MICU between the periods of January 1996 to December 2003 were reviewed. Sixty-one episodes from 54 patients were studied, of which 27 (44%) were male. RESULTS All patients were hypercapnic; 23 (38%) were ventilated. The Acute Physiological and Health Evaluation (APACHE) score II was significantly higher in the ventilated group (P<0.0001). The pH was significantly lower and PaCO2 was significantly higher in the ventilated group (P<0.0001). All patients survived. Only 42% of patients our series received inhaled corticosteroids before admission. CONCLUSION Our results suggest that severe asthma requiring ICU admission is now safely managed in ICUs. Our results are comparable to recently published data on the treatment of severe asthma in the ICU. ==== Body The rate of hospital admissions for asthma has increased in recent years with potentially serious consequences,1–4 especially for those cases that require intensive care.5,6 Despite reports of increased overall asthmatic fatalities, ICU mortality has shown a favorable outcome in the last decade.6–8 This has been attributed in part to a reduction in the incidence of barotrauma from mechanical ventilation, achieved through permissive hypercapnia, and to closer monitoring.6–8 Although only a small minority of severe asthma attacks required mechanical ventilation,6 the procedure is still associated with serious complications such as barotrauma, atelectasis, mucous plugging, hypotension, endotrachial tube malposition, pneumonia or neuropathy of critical illness.9–11 As most of the previous reports of severe asthma in the ICU have come from Western Europe or the United States of America, little has been reported about severe asthma from other places, which could have different presentations. Therefore, we decided to describe our experience with severe asthma in the ICU, including management, complications and outcome. Methods This was a retrospective case analysis conducted in the medical intensive care unit (MICU) of King Khalid University Hospital (KKUH), Riyadh, Saudi Arabia. All charts of patients admitted with severe asthma between January 1996 and December 2003 were reviewed. Severe asthma was defined according to the National Heart, Lung and Blood Institute Expert Panel, as a patient who presented with severe respiratory symptoms not responding to initial inhalation therapy or intravenous (IV) steroid.12 Severe asthma was the primary reason for admission. Patients admitted with other obstructive conditions, such as bronchiectasis or chronic obstructive pulmonary disease (COPD) evident by radiographic findings and pulmonary function tests were excluded. All clinical data including age, sex, the initial symptoms, and previous hospital or ICU admissions were reviewed. The duration of each asthma attack was recorded. A history of atopy or aspirin sensitivity was recorded. The management of the patient was also reviewed. The Acute Physiological And Chronic Health Evaluation (APACHE II) score was calculated using the worst score in the first 24 hours.13 According to hospital protocol, immediately after a clinical evaluation of the patient with near fatal asthma in the emergency room, treatment was started with frequent solbutomol and ipratropium-bromide nebulisations, IV methylprednisolone (1 mg/kg body weight every 6 hours), and IV broad spectrum antibiotics if signs of respiratory tract infection were observed. Serial arterial blood gases and peak expiratory flow rate (PEFR) were done before and after starting treatment. If there was no improvement in symptoms, PEFR or blood gases, patients were transferred to MICU for further management. If the patient deteriorated further as evidenced by a decreased level of consciousness or by developing cardiorespiratory arrest despite the above therapy, endotracheal intubation was considered either in the emergency room or in MICU. Ventilated patients were put mainly on volume-cycled mode. Four patients were ventilated using pressure-regulated volume control mode. The duration of mechanical ventilation was recorded. Also, the duration of muscle relaxant use was calculated in patients who were intubated and received neuromuscular blockade. Once the clinical status of these patients improved based on PO2, PCO2, pH and hemodynamics, extubation was considered. Hypercapnia was defined as a PaCO2 ≥ 45 mm Hg on initial blood gases.14 Sepsis was defined according to the guidelines of American College of Chest Physicians/Society of Critical Care Medicine.15 Complications were recorded. A favorable outcome was defined as discharge from the hospital. Statistical analysis was performed using Student’s t test for continuous variables and chi-square tests for categorical variables. A P value equal or less than 0.05 was considered statistically significant. Results Fifty-four patients with 62 episodes of acute severe asthma were admitted to the MICU. The mean age of the patients was 39±19 years (range, 15–56 years). These admissions represented 0.4% of total admissions throughout the period, January 1996 to December 2003. One patient file was missing and was therefore excluded. There were 27 (44%) males and all patients survived ICU and were discharged home. Demographic and clinical variables for the 61 asthmatic patients are shown in Table 1. There were no statistically significant differences in these variables between ventilated and non-ventilated patients. Table 2 shows additional clinical variables of non-ventilated and ventilated patients. There was no statistically significant difference between the groups in term of asthma duration, duration of attack, respiratory rate or blood pressure on admission. The groups were also not different in peak expiratory flow rate (PEFR). However, the APACHE II score was significantly lower in the non-ventilated group (P value <0.0001). The pH was significantly lower in the ventilated group and PCO2 was significantly higher (P<0.0001) for both. Ventilated patients were tachycardic compared to those who were not ventilated (P<0.006). All patients received β2-agonist and IV corticosteroids on their initial presentation to the emergency room. The mean duration of ventilation was 3.2±3.4 days. Muscle relaxant was used in 18 ventilated patients and the mean duration was 12.56 hours (range, 4–30 hours). The range of ICU stay was 1 day to 21 days with mean of 5.6±3.5 days. Eight patients from the ventilated group and ten patients from the nonventilated group (statistically nonsignificant difference) received subcutaneous epinepherine 1:1000 when they did not respond to the initial inhalation therapy. Three patients received IV salbutamol and 2 patients received continuous IV ketamine for 24 hours. Twenty-five patients, all in the intubated group, had complications. Four (6%) patients had barotrauma, 8 (13%) hypokalemia, 2 (3%) supra-venticular tachycardia, 8 (13%) lactic acidosis, 2 (3%) sepsis and 1 (1.6%) had myopathy. Discussion We described the clinical presentation, ICU management and outcome of patients with severe asthma. All of our patients made a complete recovery and were discharged home. Our results suggest that patients with severe asthma can be managed safely in the ICU and have a favorable outcome. Earlier studies had shown mortality figures as high as 38%.5 In a retrospective study by Mountain et al in 1998, who reported on 229 patients admitted to the ICU, a third were hypercapenic; only 5 patients were ventilated and they reported no mortality.6 Almost all reports in the last decade have shown a favorable outcome.6–8,16,17 Braun et al reported no mortality following 80 episodes of severe asthma and they attributed their excellent outcome to close monitoring and repetitive of blood gas analysis.8 A recent study from the UK attributed the improved survival to repetitive bronchoscopic airway toilet and reduction of airway pressure. This improvement in survival happened despite an increased rate of mechanical ventilation.17 All our patients were hypercapenic and a third were mechanically ventilated using volume-cycled mode, allowing permissive hypercapnia to reduce peak airway pressure below 40 mm Hg as previously recommended.18 Four of our patients were successfully ventilated using pressure-regulated volume control mode, which assured adequate tidal volume with minimal peak airway pressure, although the mean airway pressure could have been high. This mode was recently used in pediatric asthmatic patients.19 We believe the reduction in airway pressure contributed to the improved survival in our patients. The other factor that contributed to the good outcome was the absence of anoxic brain damage. Earlier data had suggested that most asthma fatalities occur at home or on arrival to the emergency room. As some of these patients were subsequently admitted to the ICU with anoxic brain damage, this lead to the alteration of the overall asthma outcome in the ICU.8,18 The APACHE II score was significantly higher in the ventilated group compared to the non-ventilated group (P<0.0001). This reflects the rapid deterioration in the physiological status of the ventilated group, requiring intubation and mechanical ventilation, shortly after their admission. Wasserfallen et al described a group of asthmatics who deteriorated rather quickly and had sudden asphyxic asthma with hypercapnia requiring intubation.20 This suggests that patients with severe asthma and a higher APACHE II score have a greater chance of intubation. Recent published studies have also shown that a high APACHE score in status asthmaticus is associated with prolonged hospitalization and death.21,22 Inadequate therapy and poor patient compliance are well known factors that precipitate severe asthma attacks.23 Among our patients, only 31% were regularly attending a follow up clinic and only 42% were receiving inhaled corticosteroids. This highlights the inadequate therapy for asthma in this series of patients, despite the recent implementation of a National Asthma Program in Saudi Arabia. The effectiveness of parenteral β-agonists has been debated, and there is a paucity of information concerning their use in severe asthma.24,25 Bloomfield et al compared intravenous β-agonist to inhaled salbutamol using a double blind, cross-over design and concluded that the two regimes were equally effective.24 On the other hand, Williams et al have shown that a parenteral β-agonist resulted in more significant improvement in peak expiratory flow rate (PEFR) compared with nebulized β-agonist.25 A significant number of our patients were given a subcutaneous β-agonist, which may have averted the need for mechanical ventilation. Apart from sinus tachycardia and hypokalemia, we encountered no other significant side effects. We therefore support the recommendation for using a parenteral β-agonist in severe asthma.26 Myopathy was documented in one patient who had a history of left lower lobectomy requiring mechanical ventilation for 12 days. Previous studies have shown that up to 30% of athmatics subjected to prolonged nondepolarizing neuromuscular blocking agents developed myopathy and muscle weakness.27,28 This complication occurred in 1.6% of our patients. This is attributed, we believe, to the short period of ventilation and limited use of neuromuscular blockade. In summary, the findings of this study are in agreement with recent reports of low mortality in severe asthmatics managed in the ICU. Aggressive therapy with non-invasive modalities should not be delayed. However, should mechanical ventilation be needed, attention should be given to reducing the airway pressure, even at the price of permissive hypercapnia. Table 1 Demographic and clinical variables of 61 ventilated and non-ventilated severe asthmatic patients treated in the medical intensive care unit. Study Variables Ventilation Test statistic P value No N = 38 (%) Yes N = 23 (%) Sex - Male 14 (36.8) 13 (56.5) 1.53* 0.217 - Female 24 (63.2) 10 (43.5) - Age 34.3±18.8 43.7±19.8 − 1.86 † 0.068 Smoking 4 (10.5) - - 0.192 History of allergies 15 (39.5) 5 (21.7) 1.32 0.251 History of aspirin use 6 (15.8) 5 (21.7) - 0.398** History of NSAID use 2 (5.3) 3 (13.0) - 0.271** On inhaled steroid 14 (36.8) 12 (52.2) 0.82 0.365 Compliance with treatment 23 (60.5) 9 (39) 1.84 0.175 Used more than 3 medications 11 (28.9) 5 (21.7) 0.10 0.749 On oral steroids 7 (18.4) 4 (17.4) - 0.610 Regular follow-up 11 (28.9) 8 (34.8) 0.037 0.84 Values are mean±standard deviation. * Chi-square; ** Fisher’s Exact test P value; † t value; NSAID: Non-steroidal anti-inflammatory drug Table 2 Additional clinical variables of 61 ventilated and non-ventilated severe asthmatic patients treated in the medical intensive care unit. Study Variables Ventilation t P value No n=38 Yes n=23 Duration of asthma (years) 8.6±7 9.8±6.7 −0.67 0.463 Duration of attacks (hours) 70.3±93 87.4±166 −0.52 0.762 Heart rate 122.9±21.3 99.7±42 2.85 0.006 Systolic blood pressure 127±21.5 134±50 −0.74 0.46 pH 7.3±0.096 7.0±0.095 10.13 <0.0001 PaCO2 50.7±11.8 86.5±22 −8.32 <0.0001 PaO2 76.7±40 84±74 −0.50 0.62 HCO3 23±5.8 23.8±5.5 −0.55 0.58 PEFR 115±110 95.6±99 0.69 0.49 APACHE II score 9.0±5.7 22±8 −7.0 <0.0001 Values are mean±standard deviation. PEFR: peak expiratory flow rate; APACHE: Acute Physiological and Chronic Health Evaluation ==== Refs References 1 Sly Rm Increased in deaths from asthma Ann Allergy 1984 53 20 25 6742521 2 Benatar SR Fatal asthma NEJM 1986 314 423 428 3511379 3 Robin ED Death from bronchial asthma Chest 1998 93 614 618 4 Williams MH JR Increase severity of asthma NEJM 1989 1015 5 Scoggin CH Sahn SA Petty TL Status asthmaticus: A nine-year experience JAMA 1977 238 1158 578161 6 Mountain R Sahn S Clinical features and outcome in patients with acute asthma presenting with hypercapnia Am Rev Respir Dis 1988 138 535 539 3202409 7 Belleome R McLaughlin P Tai E Parkin G Asthma requiring mechanical ventilation: a low mortality approach Chest 1994 105 3 891 6 8131559 8 Braman SS Kaemmerlen JY Intensive care status asthmaticus: A ten-year experience JAMA 1990 264 266 9 Picado C Montserrat JM Roca J Mechanical ventilation in severe exacerbation of asthma: Study of 26 cases with sex deaths Eur J Respir Dis 1983 64 102 7 6832248 10 Griffin D Fairman N Coursin D Acute myopathy during treatment of status asthmaticus with corticosteroids and steroidal muscle relaxants Chest 1992 102 510 4 1386568 11 Leatherman JW Fluegel WL Darid WS Muscle weakness in mechanically ventilated patients with severe asthma Am J Respir Crit Care Med 1996 153 1686 90 8630621 12 National Asthma Education Report: Expert Panel Report Guidelines for the diagnosis and management of asthma US Department of Health and Human Services Bethesda 1991 1 8 13 Knous WA Droper EA Wagner DP APACHE II: A severity of disease classification system Crit Care Med 1985 13 818 829 3928249 14 Salmeron S Brochard L Mal H Nebulized versus intravenous albuterol in hypercapnic acute asthma. A multicenter, double-blind, randomized study Am J Respir Crit Care Med 1994 6 149 6 1466 70 8004299 15 Bone RC Balk RA Cerra FB Definition for signs and organ failure and guidelines for the use of innovative therapies in sepsis: The American College of Chest Physician/Society of Critical Care Medicine (ACCP/SCCM) consensus conference committee Chest 1992 101 1644 1655 1303622 16 Pacht ER Lingo S St John RC Clinical Features, Management and Outcome of patients with severe asthma admitted to the intensive care unit J Asthma 1955 32 5 373 377 17 Kearney SE Graham DR Athertan ST Acute severe asthma treated by mechanical ventilation: A comparison of the changing characteristics over a 17-year period Resp Medicine 1998 92 716 721 18 Darioli R Perret C Mechanical controlled ventilation in status asthmaticus Am Rev Respir Dis 1984 129 385 6703497 19 Werner HA Status Asthmaticus in children Chest 2001 119 1913 1929 11399724 20 Wasserfaleen JB Schaller MD Feihl F Sudden asphyxic asthma: A distinct entity? Am Rev Respir Dis 1990 142 108 111 2368957 21 Afessa B Morales I Cury J Clinical course and outcome of patients admitted to ICU for status asthmaticus Chest 2001 20 1616 1621 22 Gehlbach B Kress JP Kahn J DeRuiter C Pohlman A Hall J Correlates of prolonged hospitalization in inner city patients receiving non-invasive and invasive positive pressure ventilation for status asthmaticus Chest 2002 22 1709 1714 23 Birkhead G Attaway NJ Strunk RC Townsend MC Teutsch S Investigation of cluster of deaths of adolescents from asthma: Evidence implicating inadequate treatment and poor patient adherence with medications J Allergy Clin Immunol 1989 84 484 91 2794293 24 Bloomfield P Carmichael J Petrie GR Comparison of salbutamol given intravenously and by intermittent positive pressure breathing in life-threatening asthma BMJ 1979 1 848 850 373852 25 Williams S Seaton A Intravenous or inhaled salbutamol in severe acute asthma? Thorax 1977 32 555 558 594935 26 Manthous CA Management of severe exacerbations of Asthma (Review) Am J Med 1955 99 298 27 Griffin D Fairman N Coursin D Acute myopathy during treatment of status asthmaticus with corticosteroids and steroid muscle relaxants Chest 1992 102 510 4 1386568 28 Leatherman JW Fluegel WL David WS Muscle weakness in mechanically ventilated patients with severe asthma Am J Respir Crit Care Med 1996 153 1686 90 8630621