Asthma Requiring Mechanical Ventilation

Asthma Requiring Mechanical Ventilation* A Low Morbidity Approach Rinaldo Bellomo, M.D.; Peter McLaughlin, M.D.; Edmond Tai, M.D.; and Geoffrey Parkin, M.D. Study objective: There is considerable uncertainty about the clinical features, respiratory physiology, and optimal management of patients with asthma requiring mechanical ventilation. Furthermore, the ventilatory and pharmacologic management of asthma requiring mechanical ventilation remain controversial. We hypothesized (I) that there are clinically identifiable and pathophysiologically different subgroups presenting with asthma requiring ventilation; (2) that lower dose steroid therapy ( < 400 mgld intravenous hydrocortisone) is adequate; (3) that permissive hypercapnia is safe; (4) that prolonged paralysis is generally unnecessary; and (5) that clinical outcome would be favorable in patients treated with this approach. Design: Review of medical records and intensive care charts and statistical analysis of findings. Setting: ICU of tertiary institution. Patients: Thirty-five consecutive cases of life-threatening asthma requiring mechanic ventilation. Results: Three clinical subgroups of ventilation-requiring asthmatics could be identified. Those presenting with steady deterioration (10), those with unstable asthma followed by a sudden "dip" (I6), and those with a sudden unexpected dip (9). Patients in the first group had a significantly lower PaC01 (p
higher PaC01 (p < O.Ol) and required ventilation for a shorter period. Those in the third group had an intermediate PaC01 level before intubation and the shortest period (p < O.OI) of mechanical ventilation. Five patients experienced their sudden dip after ingesting aspirin. Ten cases received "high" dose hydrocortisone therapy (mean: 980 mg/24 h), and 25 received lower dose hydrocortisone (mean: 34I mg/24 h). No differences in illness severity at presentation or outome could be detected between these two groups. Mean duration of ventilatory support was 36 h and mean duration of the ICU stay 52. I h. Muscle relaxation was used in I2 patients for a mean period of I 1.1 h. One patient was brain dead on arrival. All others survived. Conclusions: Life threatening asthma is an endpoint for several different clinical patterns of disease. No major clinical advantage could be found in our group of patients when high-dose steroids were used. Longterm use of muscle relaxants and prolonged mechanic ventilation are rarely needed in the management of patients with life-threatening asthma and excellent results can be achieved with a relatively simple management strategy. (Chest 1994; 105: 891-96)

Asthma requiring intubation and artificial ventilation is a dramatic complication of a common illness. Fortunately, it affects relatively few patients. This hinders the performance of controlled trials of therapeutic protocols . Divergent outcomes have been previously reported in this circumstance 1• 7 using different medication schedules and diverse ventilatory techniques . Controversy thus surrounds the management of these patients. At this institution, excellent outcomes have been obtained with a relatively simple approach to this problem . This study analyzes the clinical features of patients seen at our institution over 7 years and the consequences of a management style characterized by the avoidance of extremely high doses of steroids and complex ventilatory strategies. It also sought to establish whether differing clinical presentations and clinical courses suggest the existence of discrete subgroups among patients presenting with life-threatening asthma.

admissions to the ICU for artificial ventilation because of lifethreatening acute asthma were reviewed. Detailed information was obtained from their emergency department and ICU charts. The information obtained included the following: age and gender; previous medications for asthma; physical examination findings; pattern of clinical presentation (steady deterioration, unstable asthma followed by sudden "dip," and sudden dip <3 h) as recently described;" possible precipitating factors; medications and arterial blood gases values before and after intubation; dose of steroids administered over 24-h, use and duration of use of muscle relaxants; complications; time on ventilator; and time in the intensive care and in the hospital. All patients were treated with intravenous (IV) steroids, IV aminophylline infusion, and hourly to two hourly nebulized salbutamol with or without ipratropium bromide. IV or endotracheal salbutamol or adrenaline (or both) were used in some patients. Ventilation was performed with a volume-cycled ventilator using a low respiratory rate (8 to 10 cycles/min), assist control mode, tidal volumes of 8 to 10 ml!kg, and with the acceptance of hypercapnia and respiratory acidosis. Flow rates were kept above 70 Umin and I toE ratios at 1:2 or 1:3. Statistical analysis of data was carried out using the Wilcoxon rank sum test for non normally distributed data and Fisher's exact test for nominal data.

METIIODS

The medical records of 34 patients requiring a total of 35 *From the Department of Respiratory Medicine and Intensive Care Unit, Monash Medical Centre, Clayton, Victoria, Australia. Manuseript reeeived Mard1 9, 1993; revision at·cepted July l.

presentation, but required ventilation for longer peri-

ods. Those in the second group had a significantly

RESULTS

Thirty-four patients were studied who presented with 35 attacks of near fatal asthma requiring meCHEST I 105 I 3 I MARCH, 1994

891

Table 1-&alurea of Cases of Near-Fatal Anhma• Presentation steady deterioration unstable asthma followed by sudden dip sudden unexpected dip Preadmission therapy inhaled PRN salbutamol inhaled regular salbutamol oral theophylline low dose (<800 j.Lg/d) inhaled steroids high dose (>800 j.Lgld) inhaled steroids low dose (<10 mgld) oral steroids high dose (> 10 mgld) oral steroids mean PaCO, at presentation mean pH at presentation A-a gradient at presentation Pa0/F1o1 ratio at presentation mean HCO, at presentation

10 16 9 19 16 23 14 1

7 4 87mm Hg (r 43-190) 7.09 (r6.87-7.36) 205mm Hg (r39-634)

231 (r 50-530) 20.6mmoi!L (r 11-30)

•Mean age=39.7 yr; Sex= 16m, 18 f.

chanica! ventilation . Their mean age and clinical features at presentation are summarized in Table 1. Precipitating factors were detectable in 23 cases (infection : 13; notable allergen exposure: 3; occupational exposure: 2; drug reaction : 5). The pattern of presentation could be divided into 3 groups (Table 1). Ten cases presented after steady deterioration of their asthma over >3 days; 16 experienced a sudden deterioration (over hours) after a few days of increasingly symptomatic asthma; and 9 showed a sudden dramatic deterioration over hours. No significant differences could be found when each group was compared with both other groups for gender distribution, age, triggering factors, pH at presentation, days in the hospital, time spent in intensive care, or dose of hydrocortisone received. Analysis of PaC0 2 at presentation, however, showed that those with unstable asthma followed by a sudden dip had a significantly higher mean PaC0 2 than the other patients (105.1_ 10.7 mm Hg vs 72.9 _ 6.2 mm Hg; p < 0.02). Patients presenting after a sudden dip required ventilation for a significantly shorter time (mean: 11.4 < 2.3 h vs 45.0 < 17.2 h; p < 0.01). Interestingly, five of 25 cases of patients experiencing a sudden deterioration gave a history of a life-threatening dip after aspirin ingestion . Three of these patients belonged to the sudden dip group. No such history of probable drug reaction could be elicited in those presenting after a steady deterioration. The features of these three subgroups are summarized in Table 2. The improvement of patients after intubation was generally rapid (Table 3). All treated patients sur892

Table !-Clinical &aturea of Three Subgroups of Mechtmical Ventiltmon Requiring Aathmatica at Pruentotion•

s At Presentation Mean age Sex Mean PaCO, (mm Hg) Mean pH Mean HCO, (mmoi!L) A-a gradient (mm Hg) PaOif'lo, Course Hydrocortisone dose (mean) (mglday) h of ventilation h in ICU d in hospital

41.6 (r15-70) 8f; 2m 65.7 (UD vs others 7.19

23

UD

SD

38.0 (rl8-69) 6f;9m 105.1 p<0.02) 7.03 19

42. 1 (r24-62) 4f; 5m 81 7. 1 20.4

NS NS

250 187 194 NS (95% CI :r 128) (95% Cl :r 44) (95% CI :r 113) 199 216 275 NS (95% CI :r 76) (95% CI :r 78) (95% CI :r 97) 440

596

55.6 38 (SD vs others p<0.01) 77.3 53.5 15.9 7

516

NS

11.4 24.9 6 .2

NS NS

•s = steady deterioration; U D

= unstable asthma followed by dip; SD =sudden unexpected dip; NS =not significant; Cl =confidence interval.

vived to discharge from hospital. This is despite the fact that this group of patients had very severe asthma (two cardiac arrests in the ambulance; eight respiratory arrests either at home, in the ambulance, or just on arrival in the emergency department; one episode of epilepsy seizure of probable hypoxic origin ; one episode of broad complex tachycardia also in the ambulance) . Nine patients were intubated in the emergency department because of imminent respiratory arrest. Our philosophy regarding intubation as applied to these patients requires some discussion. The safest approach to endotracheal intubation in an asthmatic patient may be the technique of "awake" intubation . After the appropriate use of local anaesthesia, intubation Table 3-0veraU Clinical Coune of lbtienta with Near Fatal Anhma H on ventilator (mean) 36.1 (95% Cl 15.1-47.1) 11.1 (95% CI 4.8-17.1) H on muscle relaxants (mean) 52. 1 (95% C1 28.5-55.5) H in ICU (mean) (95% CI 5.8-13) 9.4 D in hospital (mean) (95% Cl 5.1-9.5) 7.3 H to normal PaCO, (mean) Hourly fall in PaCO,, mm Hg (mean) 9.2 (95% Cl 5 .7-12.7) 7.2 (95% Cl 5 .0-9.4) H to normal pH Change in Pa01f'lo1 from presentation + 100 (95% 48-152) to normal PaCO, (mean) Clinically evident myopathy 1 case Hypotension at intubation 4 cases Pneumothorax 3 cases Outcome 34 discharges from hospital; 1case of brain death before ventilation. Asthma Requiring Mechanical Ventilialion (Bellomo

et al)

P02 mmHg PC02 mmHg 600 r - - - - - - - - - - - - - - - - , 200

150

450

300

150

50

OL.....JL......JL.......J..-J--&---L--L--L....L.......&....--'-....L..-'-....&.......L....IO

-4

0

4

8

12

16

20

24

28

Time (hours)

P02 mmHg PC02 mmHg 600 r------------------------------,200

'

450

150

'

• P0 2 100 "'PC0 2

300

150

50

OL--L.....JL......JL.......JL.......J--'---L---L--L....L.......L.--'-....L..-'-..J.....Jo

-4

0

4

8

12

16

20

24

28

Time (hours) Fl<:t:IIE I. Graphs from two patients showing a typical slow rate of fall in the PaC0 1 .

can be performed transnasally or orally, with or without the aid of a bronchoscope. Intravenous fluids (stable plasma protein solution) are useful in maintaining right ventricular filling and cardiac output. This was the approach used in the majority of our patients. If sedation is believed to be necessary, a small dose of a benzodiazepine or morphine is usually sufficient. Muscle relaxation can be rapidly and safely achieved with suxamethonium. After intubation, there frequently is an "irresistible" desire to manually ventilate the patient with vigor and enthusiasm. Such behavior is usually precipitated by the frequent observation of a fall in blood pressure and oxygen saturation associated with intubation and the administration of preintubation agents. Such temptation should be resisted. Fluids should be administered to increase cardiac output and manual ventilation should be slow (8 to 10 breaths/min), deliberate, and at low volumes. A tape should be placed around the thorax

to detect increasing chest expansion . All patients received IV steroids in the form of hydrocortisone, according to the orders of the managing clinician. Two patients received 1 g of methylprednisolone early in their treatment. Twentythree patients received IV steroids before intubation. In the other 12 cases, steroids were given immediately after intubation. Patients could be divided into two groups according to the amount of steroids received every 24 h: the "higher dose" group(> 400 mg hydrocortisone/d) which included 10 patients, and the "lower dose" group of 25 cases ( < 400 mg hydrocortisone/d) . Disease severity was assessed by preintubation PaC0 2 , Pa0 2 :Fio 2 ratio, A-a gradient, pH, clinical features, presentation, preadmission therapy, and emergency department medications. No statistically significant difference was found. The high dose group received substantially more steroids (mean: 980 mg/d vs 341 mg/d) (p < 0.001). No differences in duration of ventilation, time spent in intensive care, or duration of hospitalization were seen. No other clinical benefits could be shown . When eight patients who received > 1 g of IV hydrocortisone every 24 h (mean: 1,106 mg) were compared with 27 cases receiving a mean of less than 400 mg/d (353 mg), no difference in illness severity or outcome could be shown. The IV aminophylline was started before intubation in all but eight cases and was later administered to all patients. Salbutamol was administered by oxygen driven nebulization to 29 cases before intubation and was given 1 to 2 hourly (5 mg nebulized) thereafter. Seven patients received IV adrenaline before or around the time of intubation, but none thereafter. In 3 cases, adrenaline was administered endotracheally. In another 10 cases, endotracheal salbutamol was administered. Ipratropium bromide was administered via nebulizer to 9 patients before intubation and was continued thereafter in all cases. Suxamethonium (succinylcholine) was used for the endotracheal intubation of 17 patients. No paralytic agents were used for the other 18 cases. Sedation for endotracheal intubation was used in 17 cases. Agents used included diazepam (6), midazolam (3), ketamine (3), morphine (2), and thiopentone (3). After intubation, sedation was usually maintained with either a benzodiazepine ( 14) or morphine (14). Sedation was not required in the remaining cases. Muscle relaxation was maintained with either vecuronium (3) or pancuronium (9). The remaining patients did not require the use of muscle relaxing agents after intubation. Halothane was administered to three patients because of extremely severe bronchospasm in the hope of accelerating recovery. A number of complications occurred in associaCHEST I 105 I 3 I MARCH, 1994

893

tion with mechanical ventilation. There were three cases of pneumothorax. One of these was minor and did not require active treatment. Intercostal catheter drainage was needed for the other two cases. Pneumomediastinum occurred in two patients. One patient with associated pneumonia who received prolonged ( 4 days) muscle relaxant therapy (vecuronium) and high dose steroids developed a clinically significant myopathy (weakness, creatine kinase levels greater than 3,000 IU, preserved reflexes, and myopathic electromyogram pattern). There were four episodes of hypotension complicating intubation. They all appeared to be the result of overvigorous and too rapid ventilation and responded to IV fluid boluses, prolongation of expiratory time, and diminution of tidal volume. The aim of ventilation was to maintain adequate oxygenation (always easily achieved) and accept a high PaCOg until response to therapy allowed a slow fall in PaC0 2 as seen in Figure 1. The mean time from intubation to a PaC0 2 < 45 mm Hg was 7.3 h with this approach, a mean hourly PaC0 2 fall of 9.2 mm Hg. With the fall in PaC0 2 the pH returned to normal over a similar period. Intravenous bicarbonate was not used for the acidosis seen in most patients even when severe (pH < 7.0 in 10 cases) . DISCUSSION

Asthma is a common disorder, but only in a minority of patients does it result in severe respiratory insufficiency warranting endotracheal intubation and mechanical ventilation. 1•2•6 •7•9 • 11 Why patients develop such severe asthma and whether some have unique features at presentation is a matter of continuing debate. Further, it is uncertain why some of these patients die and whether steps taken in the management of their asthma do not in fact contribute to an unfavorable outcome. 12- 14 Controversy exists about optimal techniques of intubation and the perils of the peri-intubation period.12 Once the upper airway has been secured, there is debate about the most appropriate ventilatory techniques, 14 17 the need for and duration of muscle relaxant therapy, 18-20 the need for bicarbonate and for a rapid or gradual normalization of the Pco 2 , and the dose of steroids that is associated with the most favorable outcome. 21 "25 It is unlikely that all these major issues pertaining to the management of catastrophic asthma will be resolved by any single study. It is important, nonetheless, that different management strategies and their outcomes be reported to offer therapeutic choices to clinicians. It is also useful to analyze the clinical behavior of patients with life-threatening asthma in the hope of gaining further insight into 894

possible pathogenetic mechanisms underlying this condition. The current study attempts to better define the clinical features of catastrophic asthma and point to a low-morbidity management strategy. Based on their description and on its confirmation by witnesses, patients with catastrophic asthma present in three major ways.8 One is characterized by clinical deterioration over several days ; another by a sudden dip in lung function after days of instability; and a third by a sudden attack (a "bolt from the blue"). Do these three modes of presentation define subgroups of patients with other significant differences? Overall, patients with a steady deterioration have a lower PaC0 2 at presentation, have a higher serum bicarbonate, require a longer period of ventilation, and are in the ICU and in the hospital longer. Those with unstable asthma followed by a sudden dip tend to have the highest Pco 2 , the lowest bicarbonate levels, and intermediate times on the ventilator, in the ICU and in the hospital. Finally, those with an acute attack (a bolt from the blue) have an intermediate level of PaC0 2 , and the shortest durations of ventilatory support and ICU and hospital stays . There appear to be no differences in gender and age distribution between these three subgroups. Our findings are in keeping with the concept 8 that a clinician may be dealing with three different pathogenetic mechanisms: progressively worsening inflammation; active poorly controlled inflammation followed by sudden superimposed bronchospasm; and, finally, acute predominant asphyxic bronchospasm in the setting of relatively mild background inflammation. The presence of different subpopulations may also have relevance to studies investigating steroid therapy in acute asthma. The rate of improvement differs in different subgroups and, if these are unknowingly lumped together, incorrect interpretations of therapeutic responses 22·24 may occur. Whatever the possible pathogenesis, our experience and that of others 10•26 •2i indicates that the period surrounding endotracheal inbutation is a most delicate one. Our philosophy concerning this is described in the Results section . Following connections to the ventilator, mechanical ventilation should continue slowly and at conventional to modest volumes (8 to 10 ml!kg/breath). A pulse oximeter should monitor the adequacy of oxygenation . This is rarely, if ever, a major problem if a high Fio2 (> 0.6) is used. How important is it to lower the PaC0 2 ? In our view, of little importance . There is good evidence that hypercarbia per se is not dangerous; 28 •29 in fact, permissive hypercarbia is now being proposed as a feature of a ventilatory approach to adult respiraAsthma Requiring Mechanical Ventiliation (Bellomo

et al)

tory distress syndrome (ARDS). 2v Therapy in this group of mechanically ventilated asthmatics was directed toward maintaining oxygenation, and preventing gross chest overexpansion and acute right ventricular failure. Hypercarbia was accepted until the condition responded to treatment. It is important, however, to stress that acidosis leads to a surge in endogenous catecholamines with a potential for arrhythmias; therefore, this approach may not be safe for older asthmatics or patients with a cardiac history. The fact that no patients with arrhythmias were seen in the hospital setting in our study possibly relates to the correction of hypoxemia, another powerful arrhythmogenic stimulus which may have been a major factor in the out-of-hospital cardiac arrests. Finally, seven of our patients received IV adrenaline (all patients were under 30 years of age, had been intubated, and had had their hypoxemia corrected by the administration of high concentrations of oxygen). This practice is controversial and potentially very dangerous. We currently only use salbutamol given by infusion and discourage the use of IV adrenaline. The agitation, fear, and distress associated with severe asthma often means that intubation needs to be followed by sedation to allow coordination between the ventilator and the patient's respiratory efforts. In the current series, such sedation was achieved with benzodiazepines (midazolam, diazepam, clonazepam) (16 cases) or morphine (15 cases). Our experience suggests that both drugs are safe and that concerns about histamine release secondary to morphine administration are not justified .311 Muscle relaxation using either pancuronium or vecuronium was required in 12 cases, usually for a brief period. In one case, a requirement for prolonged muscle relaxation in the context of pneumonia and the use of high dose steroids was associated with the development of a clinically significant myopathy. This complication has now been reported by others'~· 2"·'1 1 and invites extreme caution against the combined prolonged use of muscle relaxation and high dose steroid therapy. Occasionally, asthma can be so severe that other, less usual, means of bronchodilatation are sought. 32 In three of our patients, halothane was used to achieve bronchodilatation . This agent, however, is associated with the risk of hepatitis and enflorane may be a safer choice. Everyone agrees that steroids should be used in status asthmaticus. There is, however, continuing disagreement as to what dosage is best. 21 · 2s No benefit of higher dose steroid therapy was identified in our study when compared with a standard "lower-

dose" regimen as previously defined.2s We used IV aminophylline in all of our patients. Whether aminophylline offers clinically important benefits in acute asthma remains controversial. 33 In our experience, it has proved safe. No arrhythmia could be attributed to it. With respect to this issue, our findings are consistent with recent data34 suggesting that deaths in asthmatics are unlikely to he the result of cardiac arrhythmias. A number of our patients also received nebulized ipratropium bromide. This drug has recently been shown to be of benefit in acute asthma.JS- 37 No difference was found in illness severity or speed of resolution when these patients were compared with the remaining asthmatics in this study. Our results should be compared with those of other studies so far reported in the 90s. A 22 percent mortality and an 18.7 percent incidence of pneumothorax was recently reported in a US series of 32 episodes of asthma requiring mechanical ventilation.' Patients in this study did not appear more severely ill than in our cohort (mean preintubation pH 7.31 vs 7.09 in our series; mean preintubation PaC0 2 49 mm Hg vs 87 mm Hg in our group). Mean duration of mechanical ventilation, however, was greater (77 h vs 36.1 h in our series), and these patients received high-dose steroids (methylprednisolone 60 to 125 mg IV every 6 h). A similar high-dose steroid regimen (dexamethasone 10 mg IV every 8 h or hydrocortisone 2.50 mg IV every 6 h) was used by Douglass et al. 31 They experienced two asthma deaths in 25 cases (8 percent), and 4 cases of clinically severe myopathy ( 1 in our series). Illness severity was similar to ours: mean preintubation pH was 7.07 vs 7.09; mean PaC0 2 before intubation was 87.2 mm Hg vs 87.0 mm Hg. Their patients, however, were paralyzed longer (mean duration of paralysis: 60 h vs 11.1 h) and spent more time on the ventilator (mean duration of mechanical ventilation: 158.4 h vs 36.1 h) . Such comparisons highlight our growing concern about the consequences of high dose steroids and prolonged use of muscle relaxing agents. Despite its limitations, therefore, our study suggests that there may be different pathogenetic mechanisms involved in patients with catastrophic asthma. These may need to be taken into account in future comparisons of treatment regimes. Our experience with management of asthma requiring mechanical ventilation, as reported here, also suggests that little sedation before intubation, slow, low-volume, manual ventilation in the emergency room before mechanical ventilation, muscle relaxation for a limited time (hours), a slow rate of mechanical ventilation, modest to conventional tidal volumes, the acceptance of hypercarbia, and caution with steroid dosages repCHEST I 105 I 3 I MARCH. 1994

895

resent a simple and safe approach for the patient with life-threatening asthma. The outcomes of future approaches using more complex interventionist and pharmacologically aggressive strategies should be judged in the light of our results. ACKNOWLEDGMENTS: The authors thank Ms. Jenny Neil's for her excellent secretarial assistance and Dr. Neif Boyce for his constructive advice. REFERENCES

Scoggin CH, Sahn SA, Petty TL. Status asthmaticus: a nineyear experience. JAMA 1977; 238:1158-62 2 Westerman DE, Benatar SR, Potgieter PD, Ferguson AD. Identification of the high risk asthmatic patient. Am J Med 1979; 66:565-72 3 Picado C, Montserrat JM, Roca J. Mechanical ventilation in severe exacerbation of asthma. Eur J Respir Dis 1983; 64:102-07 4 Darioli R, Perret C. Mechanical controlled hypoventilation in status asthmaticus. Am Rev Respir Dis 1984; 129:385-87 5 Higgins B, Greening AP, Crompton GK. Assisted ventilation in severe acute asthma. Thorax 1986; 41:464-67 6 Luksza AR, Smith P, Coakley J, Gordon IJ, Atherton ST. Acute severe asthma treated by mechanical ventilation: 10 years' experience from a district general hospital. Thorax 1986; 41 :459-63 7 Mansell JK, Strogner SW, Petrini MF, Norman JR. Mechanical ventilation in patients with acute severe asthma. Am J Med 1990; 89:42-48 8 Wasserfallen J-B, Schaller M-D, Feihl F, Perret CH . Sudden asphyxic asthma: a distinct entity. Am Rev Respir Dis 1990; 142:108-11 9 Dales R, Munt P. Use of mechanical ventilation in adults with severe asthma. Can Med Assoc J 1984; 130:391-95 10 Webb AK, Bilton AH , Hanson GC: Severe bronchial asthma requiring ventilation: a review of 20 cases and advice on management. Postgrad Med J 1979; 55:161-70 11 Hetzel MR. Clark TJH, Branthwaite MA: Asthma: analysis of sudden deaths and ventilatory arrests in hospital. BMJ 1977; 1:808-11 12 Rosengarten PL. Tuxen DV, Dziukas L, Scheinkestel C, Merrett K, Bowes G. Circulatory arrest induced by intermittent positive pressure ventilation in a patient with severe asthma. Anesth lnt Care 1991; 19:118-21 13 Sonia Buist A. Asthma mortality: what have we learned? J All Clin Immunol 1989; 84:275-83 14 Tuxen DV. Detrimental effects of positive end-expiratory pressure and controlled mechanical ventilation in patients with severe airflow obstruction . Am Rev Respir Dis 1989; 140:5-9 15 Qvist J. Andersen JB , Pemberton M, Bennike K-A. Highlevel PEEP in severe asthma. N Eng! J Med 1982; 307:134748 16 Marini JJ. ed. Should PEEP be used in airflow obstruction. Am Rev Respir Dis 1989; 140:1-3 17 Tuxen DV, Lane S. The effects of ventilatory pattern on hyperinflation, airway pressures and circulation in mechanical ventilation of patients with severe air-flow obstruction.

896

Am Rev Respir Dis 1987; 136:872-79 18 Kuppfer Y, Okreut DC, Twersky RA, Tessler S. Disuse atrophy in a ventilated patient with status asthmaticus receiving neuromuscular blockade. Crit Care Med 1987; 15:79596 19 Shee CD. Risk factors for hydrocortisone myopathy in acute severe asthma. Respir Med 1990; 84 :229-33 20 Margolis BD, Khachikian D, Friedman Y, Garrard C. Prolonged reversible quadriparesis in mechanically ventilated patients who received long-term infusions of vecuronium. Chest 1991; 10:877-78 21 Raimondi AC, Figueroa-Casas JC, Roncoroni AJ . Comparison between high and moderate doses of hydrocortisone in the treatment of status asthmaticus. Chest 1986; 89:832-35 22 Haskell RJ , Wong BM, Hansen JE. A double-blind, randomized clinical trial of methylprednisolone in status asthmaticus. Arch Intern Med 1983; 143:1324-27 23 Harfi H, Harrissian AS, Crawford LV. Treatment of status asthmaticus in children with high doses and conventional doses of methylprednisolone. Pediatrics 1978; 61 :829-31 24 Tanaka RM, Santiago SM, Kuhn GJ, Williams RE, Klauster Meyer WB. Intravenous methylprednisolone in adults in status asthmaticus: comparison of two dosages. Chest 1982; 84:438-40 25 Britton MG, Collins JV, Brown D, Fairhurst NPA, Lambert RG. High dose corticosteroids in severe acute asthma. BMJ 1976; 2:73-74 26 Halttunen PE, Luomanm;auakikk, Takkunen 0 , Vilijanen AA. Management of severe bronchial asthma in an intensive care unit. Ann Clin Res 1980; 12:109-11 27 Riding WD, Ambiaragerr M. Resuscitation of the moribund asthmatic. Postgrad Med J 1967; 43:234-43 28 Petty TL. CO, can be good for you. Respir Management 1987; 17:7-66 29 Hickling KG , Henderson SJ, Jackson R. Low mortality associated with low volume pressure limited ventilation with permissive hypercapnia in severe adult respiratory distress syndrome. Intensive Care Med 1990; 16:372-77 30 Jaffe JH , Martin WR. Opioid analgesics and antagonists. In: Goodman Gilman A. eds. The pharmacological basis of therapeutics . 7th ed. NY: Macmillan Publishing Co, 1985; 502 31 Douglass JA, Tuxen DV, Horne M, Sheinkestel CD, Weinman M, Czarny D, Bowes G. Myopathy in severe asthma. Am Rev Respir Dis 1992; 146:517-19 32 Johnston RG, NoseworthyTW, Friesen EG, Yule HA, Shustak A. Isoflurane therapy for status asthamaticus in children and adults. Chest 1990; 97:698-701 33 Littenberg B. Aminophylline treatment in severe, acute asthma. A meta-analysis. JAMA 1988; 259:1678-84 34 Molfino N, Nannini L, Martelli A, Slutsky AS . Respiratory arrest in near fatal asthma. N Eng! J Med 1991 ; 324:285-88 35 Ward MJ, Fentem PH, Roderick Smith WH, Davies D. lpratropium bromide in acute asthma. BMJ 1981; 282:598600 36 Rebuck AS, Chapman KR , Abboud R, Pare PD. Kreisman H, Wolkove N. Nebulized anticholinergic and sympathomimetic treatment in asthma and chronic obstructive airways disease in the Emergency Room . Am J Med 1987; 82:59-64 37 Bryant DH . Nebulized ipratropium bromide in the treatment of acute asthma. Chest 1985; 88:24-29

Asthma Requiring Mechanical Ventiliation (Bellomo eta/)