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Is there a role for inhalational anaesthetic in refractory asthma in adults?

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.
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 recoveryMorbidity outcome not evaluated. Single case report.
L. Revich, S. Grinspon et al.
1 adult patient with refractory asthma. Intervention: Treated on ICU for 7 hours with halothane 0.5% - 2%Case report (level 4)MortalitySurvivalSingle 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 length24 hours
Total hospital stay3 days
Pulmonary function testsNormal on discharge
N. Mori, H. Nagata et al.
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 functionU&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.
2 adult patients and 2 children admitted to hospital with refractory asthma (adult patients only used in paper review). InterventionCase study (level 4)Improvement of PCO2 valuePaCO2 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 recoveryLaboratory tests reported as normal for both patients on discharge
F. Saulnier, A. Durocher et al.
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 gaspH 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 PaO2Halothane 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 pressureMean 55cm H2O pre halothane. Mean 47cm H2O post halothane. p < 0.001. Significant drop in PIP
Mean pulmonary arterial pressure30mmHg prior to halothane, 25mmHg post halothane. p < 0.005
Cardiac index (l/min/m2)No significant change (3.9 - 3.6)
Pulse113 bpm significantly reduced to 106 bpm post halothane. p < 0.01
T Schultz
26 year old female with status asthmaticus Intervention: Sevoflurane administration until patient was stable for transfer to tertiary facilityCase study (level 4)MortalitySurvivalSingle 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 intubation5 days
Total hospital stay7 days
G Mutlu, P Factor et al
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 hoursCase series (level 4)Arterial blood gasNo 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 intubation5 days (patient 2)
Length of hospital stay11 days
MortalityBoth patients survived.
H. Arakawa, T Takizawa et al.
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)pH6.98 pre anaesthetic rising to 7.2 after 120 mins of isofluraneStudy 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
pCO2105.5mmHg pre anaesthetic falling to 41.5mmHg after 120 mins of isoflurane
Duration of isoflurane therapy10 days (final 2 days with inhlaed oxotropium bromide)
Total length of intubation14 days
Mortality / MorbiditySurvived with normal blood results on discharge
F. Maltais, M. Sovilj et al.
3 patients (2 male, 1 female) with status asthmaticus refractory to conventional treatment. Intervention: Isoflurane therapy with dose tailored to each patientIndividual case control study (level 3b)RMax (maximum respiratory resistance)Maximum resistance decreased with isoflurane useOnly 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.
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 volumeIncreased 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
pH7.23 on admission to 7.41 whilst anaesthetised
pO2On admission (10L oxygen) 108 torr improved to 23.2 torr with isoflurane
pC0254 torr on admission improving to 40 torr with isoflurane
Intubation length3 days


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.


  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