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Three Part Question

In [adult patients with refractory asthma] can the use of [inhalational anaesthetic] [improve patient outcome]

Clinical Scenario

An asthmatic patient is admitted to the emergency department with severe asthma. Despite conventional treatment they are not improving. You wonder if the use of inhalational anaesthetic would have any benefit in outcome.

Search Strategy

Pubmed database

((("anesthetics, inhalation" [MeSH Terms]) OR
(("anesthetics" [All Fields]) AND ("inhalation" [All Fields]))) OR ("inhalation anesthetics" [All Fields])) OR (("inhalational" [All Fields]) AND ("anaesthetic" [All Fields]))) OR ("inhalational anaesthetic" [All Fields])) OR ("anesthetics, inhalation" [Pharmacological Action])) AND (refractory [All Fields])) AND (("asthma" [MeSH Terms]) OR ("asthma" [All Fields]))) AND (("adult" [MeSH Terms]) OR ("adult" [All Fields]))) AND "English" [Language]))

A second search was conducted also using Pubmed database
((("anesthetics, inhalation" [MeSH Terms]) OR
(("anesthetics" [All Fields]) AND ("inhalation" [All Fields]))) OR ("inhalation anesthetics" [All Fields])) OR (("inhalational" [All Fields]) AND ("anaesthetic" [All Fields]))) OR ("inhalational anaesthetic" [All Fields])) OR ("anesthetics, inhalation" [Pharmacological Action])) AND ((("status asthmaticus" [MeSH Terms]) OR (("status" [All Fields]) AND ("asthmaticus" [All Fields]))) OR ("status asthmaticus" [All Fields]))) AND (("adult" [MeSH Terms]) OR ("adult" [All Fields]))) AND ("English" [Language]))

Search Outcome

In total 20 papers were found of which 9 were irrelevent. 1 paper only had the abstract available from which no conclusions could be drawn.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
H. Thomson, N Harper et al. 2007 United Kingdom	1 adult female with refractory asthma Intervention: endotracheal intubation and inhalational isofluorane using the AnaConDa™ Anaesthetic Conserving Device.	Case report (level 4)	Full recovery		Morbidity outcome not evaluated. Single case report.
L. Revich, S. Grinspon et al. 2001 Brazil	1 adult patient with refractory asthma. Intervention: Treated on ICU for 7 hours with halothane 0.5% - 2%	Case report (level 4)	Mortality	Survival	Single patient analysis. The patient received continuous nebulized salbutamol (0.05mg/kg/h), intravenous hydrocortisone (400 mg/day), aminophylline (0.5 mg/kg/h) and AMV in the hypoventilation control mode. This patient also required treatment with dobutamine. Difficult to find single factor which accounted for recovery
			Intubation length	24 hours
			Total hospital stay	3 days
			Pulmonary function tests	Normal on discharge
N. Mori, H. Nagata et al. 1996 Japan	2 patients included: Adult male admitted to ICU following surgery. Endotracheal intubation triggered asthma attack. Inhalation of sevofluorane was started 33 h after the onset of the asthmatic attack. With inhalation of l%-3% sevofluorane, peak airway pressure decreased promptly to 16-20 cm H,O at the same tidal volume. Weaning from the ventilator was started 5 h after the start of sevofluorane and discontinued after 30 h. Patient discharged from ITU on day 5. Adult male with refractory status asthmaticus was admitted to ICU. Administration of dexamethasone and adrenaline did not lead to improvement of symptoms, so inhalation of 2% sevofluorane was started under pressure controlled ventilation with a peak airway pressure of 30 cm H,O, a frequency of 15 breaths/min, and 50% oxygen by a Servo 900C. Because adequate ventilation was not achieved, the sevofluorane concentration was increased to 4%. Sevofluorane administration was gradually reduced on day 4 and discontinued on the following day. The patient was discharged from ICU on day 8.	Case series (level 4)	Renal function	U&E's and urine output remained stable. Patient survived.	End point only considered renal function. No follow up data for either patient. Overall length of stay in hospital unknown. Single outcome measure which does not consider overall effect of inhalational anaesthetic. Discharge pulmoary function tests not mentioned
RG Johnston, TW Noseworthy et al. 1990 USA	2 adult patients and 2 children admitted to hospital with refractory asthma (adult patients only used in paper review). Intervention	Case study (level 4)	Improvement of PCO2 value	PaCO2 35mmHG on admission, deteriorating to 65mmHg after twelve hours, PCO2 35mmHG after 16 hours of isoflurane therapy (patient 1). PaCO2 165mmHg improved to 35mmHG after 34 hours isoflurane (patient 2)	Length of hospital stay not recorded Discharge physiological parameters not recorded (PEFR, ABG)
			Full recovery	Laboratory tests reported as normal for both patients on discharge
F. Saulnier, A. Durocher et al. 1990 France	12 patients (9 female, 3 male) admitted to a single unit ICU with status asthmaticus. Intervention: 1% halothane was administered to each patient for 30 minutes with physiological parameters recorded.	Prospective study (level 2)	Arterial blood gas	pH mean 7.21 increased to 7.25 post halothane. p < 0.001. PCO2 decreased from mean 82mmHg to 73 mmHg. p < 0.001. No significant change in PaO2	Halothane commenced at different times for each patient Patients not followed up long-term. No report on longterm outcome following halothane use Length of intubation, ICU or hospital stay not recorded
			Peak inspiratory pressure	Mean 55cm H2O pre halothane. Mean 47cm H2O post halothane. p < 0.001. Significant drop in PIP
			Mean pulmonary arterial pressure	30mmHg prior to halothane, 25mmHg post halothane. p < 0.005
			Cardiac index (l/min/m2)	No significant change (3.9 - 3.6)
			Pulse	113 bpm significantly reduced to 106 bpm post halothane. p < 0.01
T Schultz 2005 USA	26 year old female with status asthmaticus Intervention: Sevoflurane administration until patient was stable for transfer to tertiary facility	Case study (level 4)	Mortality	Survival	Single patient case study report from nursing staff No record of post anaesthetic arterial blood gas values or physiological parameters. No record of additional medical therapy
			Length of intubation	5 days
			Total hospital stay	7 days
G Mutlu, P Factor et al 2002 USA	2 female patients with refractory asthma requiring ventilation on ICU Intervention: Patient 1: sevoflurane administered 6 hours after intubation and ventilation. Administered for 2 hours. Patient 2: isoflurane therapy administered at 5% and reduced to between 1-2% for 30 hours	Case series (level 4)	Arterial blood gas	No improvement (patient 1) with worsening hypercapnea (pCO2 120 mm Hg pre anaesthetic 202 mm Hg post anaesthetic). Improvement in ABG (patient 2). pH improved from 6.99 to 7.07. PCO2 reduced from 212 mm Hg to 120 mmHg	Sevoflurane therapy discontinued at early stage. No evidence that sevoflurane made asthma worse. No record of dicharge pulmoary function tests Both patients had complications from asthma, including subcutaneous emphysema, pneumomediastinum and bilateral pneumothoraces (patient 1). Pneumomediastinum (patient 2).
			Length of intubation	5 days (patient 2)
			Length of hospital stay	11 days
			Mortality	Both patients survived.
H. Arakawa, T Takizawa et al. 2002 Japan	Single patient case study 19 year old female admitted with acute exacerbation of asthma unresponsive to 16 hours of medical therapy. The patient was intubated and ventilated with isoflurane therapy administered for 10 days, alongside oxotropium bromide for the last 2 days.	Case study (level 4)	pH	6.98 pre anaesthetic rising to 7.2 after 120 mins of isoflurane	Study states that effects of isoflurane, sevoflurane and halothane were all assessed during the case. No explanation fo method or duration of treatment No record of length of hospital stay No record of pulmonary function tests on discharge
			pCO2	105.5mmHg pre anaesthetic falling to 41.5mmHg after 120 mins of isoflurane
			Duration of isoflurane therapy	10 days (final 2 days with inhlaed oxotropium bromide)
			Total length of intubation	14 days
			Mortality / Morbidity	Survived with normal blood results on discharge
F. Maltais, M. Sovilj et al. 1994 Canada	3 patients (2 male, 1 female) with status asthmaticus refractory to conventional treatment. Intervention: Isoflurane therapy with dose tailored to each patient	Individual case control study (level 3b)	RMax (maximum respiratory resistance)	Maximum resistance decreased with isoflurane use	Only respiratory mechanics considered. Arterial blood gases for each patient were recorded prior to starting inhalational anesthetic but not recorded after stopping. No report of mortality or morbidity No statistics applied for significance of results
			RMin (minimum respiratory resistance)	Minimum resistance decreased with isoflurane use
			Respiratory system compliance (Crs)	No significant change with isoflurane
			Expiratory volume flow (to assess airway calibre)	Flow curve showed improvement with maximal isoflurane therapy
M. Bierman, M. Brown et al. 1986 USA	34 year old female with refractory asthma. Mechanical ventilation and full medical therapy failed to improve symptoms and the patient was transferred to the operating department and administered 1% isoflurane for 30 minutes.	Case study (level 4)	Tidal volume	Increased with isoflurane	No record of total length of hospital stay No record of pulmonary function tests on discharge No statistics applied to look for significant improvement in data values
			pH	7.23 on admission to 7.41 whilst anaesthetised
			pO2	On admission (10L oxygen) 108 torr improved to 23.2 torr with isoflurane
			pC02	54 torr on admission improving to 40 torr with isoflurane
			Intubation length	3 days
			Mortality	Survived

Comment(s)

There is adequate low level evidence which supports the use of inhalational anaesthetic in refractory asthma There is no evidence to suggest which inhalational anesthetic is best in refractory asthma The length of time the patient receives inhalational anaesthetic should be based on each individual patient and their clinical parameters

Clinical Bottom Line

In some patients with asthma, refractory to medical treatment, inhalational anesthetic should be considered.

References

1. H. Thomson, N. Harper et al. Use of the AnaConDa™ anaesthetic delivery system to treat life-threatening asthma
2. L. Revich, S. Grinspon et al. Respiratory Effects of Halothane in a Patient with Refractory Asthma
3. N. Mori, H. Nagata et al. Prolonged sevoflurane inhalation was not nephrotoxic in two patients with refractory status asthmaticus
4. RG Johnston, TW Noseworthy et al. Isoflurane therapy for status asthmaticus in children and adults
5. F. Saulnier, A. Durocher et al. Respiratory and hemodynamic effects of halothane in status asthmaticus
6. T Schultz Sevoflurane administration in status asthmaticus: a case report
7. G Mutlu, P Factor et al Severe status asthmaticus: Management with permissive hypercapnia and inhalation anesthesia
8. H. Arakawa, T Takizawa et al. Efficacy of inhaled anticholinergics and anesthesia in treatment of a patient in status asthmaticus
9. F. Maltais, M. Sovilj et al. Respiratory mechanics in status asthmaticus
10. M. Bierman, M. Brown et al. Prolonged isoflurane anesthesia in status asthmaticus