Cost-benefit analysis of
nitrous oxide in major surgery
Presenter: Dr Alison Graham
2nd year Anaesthesia Advanced Trainee
Co-Authors: Prof Paul S. Myles, Prof. Kate Leslie,
Prof. Matthew T.V. Chan, Prof. Michael J. Paech,
Dr Philip Peyton and Prof. Abdelazeem A. El. Dawlatly
Topics:
• Review ENIGMA trial
• Cost-benefit analysis
– Methods
– Results
– Limitations
– Conclusion
ENIGMA Trial
• The Avoidance of Nitrous Oxide in Major Surgery
• What are the consequences of using nitrous oxide?
30% O2 & 70% N2O
80% O2 & 20% N2
VS
ENIGMA Results
Variable
Hospital LOS,
days (IQR)
Time to eligibility to
discharge from PACU,
minutes median (IQR)
ICU admissions,
No. (%)
Nitrous-oxide
free group
Nitrous-oxide
group
p-value
7.0 (4.0 – 10.9)
7.1 (4.0 – 11.8)
0.06
84 (64 – 120)
92 (65 – 125)
0.02
122 (12%)
140 (14%)
0.3
ENIGMA Trial Results
Kaplan-Meier estimates of discharge from the intensive care unit
ENIGMA Results
Variable
Nitrous oxidefree Group
No. (%)
Nitrous oxide
Group
No. (%)
Adjusted
Odds Ratio
(95% CI)
p-value
Severe nausea or
vomiting
104 (10)
229 (23)
0.40 (0.31-0.51)
<0.001
Wound infection
77 (7.7)
106 (10)
0.72 (0.52-0.98)
0.036
Fever
275 (28)
345 (34)
0.73 (0.60-0.90)
0.003
Pneumonia
15 (1.5)
30 (3.0)
0.51 (0.27-0.97)
0.040
Atelectasis
75 (7.5)
127 (13)
0.55 (0.40-0.75)
<0.001
Pneumothorax
1 (0.1)
3 (0.3)
-
-
Myocardial
infarction
7 (0.7)
13 (1.3)
0.58 (0.22-1.50)
0.26
Thromboembolism
16 (1.6)
10 (1.0)
1.60 (0.72-3.55)
0.25
Blood transfusion
188 (19)
202 (20)
0.96 (0.75-1.21)
0.71
Stroke
1 (0.1)
1 (0.1)
-
-
Awareness
0 (0.0)
2 (0.2)
-
-
Death within 30
days
3 (0.3)
9 (0.9)
0.33 (0.09-1.22)
0.096
ENIGMA Results
Variable
Nitrous oxidefree Group
No. (%)
Nitrous oxide
Group
No. (%)
Adjusted
Odds Ratio
(95% CI)
p-value
Severe nausea or
vomiting
104 (10)
229 (23)
0.40 (0.31-0.51)
<0.001
Wound infection
77 (7.7)
106 (10)
0.72 (0.52-0.98)
0.036
Fever
275 (28)
345 (34)
0.73 (0.60-0.90)
0.003
Pneumonia
15 (1.5)
30 (3.0)
0.51 (0.27-0.97)
0.040
Atelectasis
75 (7.5)
127 (13)
0.55 (0.40-0.75)
<0.001
Pneumothorax
1 (0.1)
3 (0.3)
-
-
Myocardial
infarction
7 (0.7)
13 (1.3)
0.58 (0.22-1.50)
0.26
Thromboembolism
16 (1.6)
10 (1.0)
1.60 (0.72-3.55)
0.25
Blood transfusion
188 (19)
202 (20)
0.96 (0.75-1.21)
0.71
Stroke
1 (0.1)
1 (0.1)
-
-
Awareness
0 (0.0)
2 (0.2)
-
-
Death within 30
days
3 (0.3)
9 (0.9)
0.33 (0.09-1.22)
0.096
Criticism of the ENIGMA Trial
• “Despite the concerns regarding its adverse
effects, nitrous oxide has actually had a central
position in anesthetic practice primarily because
it is inexpensive, widely available, and has a
long-standing safety profile. The most obvious
advantage of using nitrous oxide is that it allows a
dose reduction of other anesthetic agents and
opioids, which translates into less cardiovascular
depression and significant cost reduction”
Anesthesiology 2008; 108:541-2
Cost-Benefit Analysis of the ENIGMA Trial
• What is the financial cost of using nitrous oxide?
Health economics
Health economics
Health economics
Cost Minimisation
Cost benefit - $ only
Cost effectiveness – natural units
Cost utility - QALY
Cost-Benefit Analysis of the ENIGMA Trial
• What is the financial cost of using nitrous oxide?
• From the hospital administration’s point of view
Cost-benefit N2O: variable costs
• Costs saved
– Maintenance anaesthetic
– Analgesia
– Vasopressors
• Expenses
– PONV prophylaxis
– PONV
– Infection/fever
– Pneumonia
– Atelectasis
– PACU
– ICU
– HLOS
Cost-benefit N2O: variable costs
• Costs saved
– Maintenance anaesthetic
– Analgesia
– Vasopressors
• Expenses
– PONV prophylaxis
– PONV
– Infection/fever
– Pneumonia
– Atelectasis
– PACU
– ICU
– HLOS
Contributing Cost Estimates
Contributing cost description
Estimated cost per unit
(2010 US dollars)
Gas supplies:
nitrous oxide
$0.0123/L
oxygen and medical air
$0.003/L
Induction agents:
Propofol
$1.40 per 200 mg ampoule
Thiopentone
$12.60 per 500 mg ampoule
Inhalational agents:
Sevoflurane
$11.40 MAC hour
Isoflurane
$1.50 MAC hour
Desflurane
$12.60 MAC hour
Prophylactic antiemetic therapy:
$4.95 per treatment
Contributing Cost Estimates
Estimated cost per
unit
(2010 US dollars)
Number of studies
$0.81/minute
3
$22.56 for 1 or more
episodes
7
Wound infection
$10,514/infection
30
Pneumonia
$13,439/infection
9
$2,110/day
11
Contributing cost description
PACU stay
PONV
ICU stay
ENIGMA Cost-Benefit Analysis: Results
Estimated costs per patient (US dollars), Mean ± SD
Anaesthetic
drugs
Bed days
Complications
Total costs
Nitrous oxide-free
Group
(n = 997)
Nitrous oxide
Group
(n = 1,015)
p-value
27 ± 22
26 ± 22
0.16
12,793 ± 11,547
14,685 ± 18,718
0.005
1,017 ± 3,496
1,500 ± 4,210
0.006
13,837 ± 13,256
16,203 ± 20,842
0.002
ENIGMA Cost-Benefit Analysis:
Sensitivity Analysis
Estimated costs per patient (US dollars), Mean ± SD
Nitrous oxidefree group
(n = 997)
Nitrous oxide
group
(n = 1,015)
p-value
13,837 ± 13,256
16,203 ± 20,842
0.002
(i) Wound infection
13,228 ± 12,421
15,379 ± 19,902
0.004
(ii) Pneumonia
13,686 ± 12,734
15,915 ± 20,136
0.003
4,242 ± 5,301
5,187 ± 7,487
0.001
(i) Wound infection
16,273 ± 18,712
19,500 ± 26,536
0.002
(ii) Pneumonia
14,444 ± 16,127
17,356 ± 24,631
0.002
(iii) Bed days
52,218 ± 47,604
60,269 ± 76,765
0.005
Total estimated costs (base line)
¼ of component costs
(iii) Bed days
4x component costs
Cost-Benefit Analysis Limitations
• Estimated costs (but the statistics are real)
• Hospital perspective only
• Use of published estimates of costs
– Precedent studies mostly from developed countries
– No discrimination on methods
• Variable costs only included
• PACU costs controversial
Conclusions
• There are significant additional costs with N2O use
• No compelling argument to use N2O on the basis that it
is an inexpensive drug
Questions
Sensitivity Analysis
Nitrous oxidefree Group
(n = 997)
Nitrous oxide
Group
(n = 1,015)
P value
13,837 ± 13,256
16,203 ± 20,842
0.002
i. Wound infection
13,228 ± 12,421
15,379 ± 19,902
0.004
ii. Pneumonia
13,686 ± 12,734
15,915 ± 20,136
0.003
4,242 ± 5,301
5,187 ± 7,487
0.001
i. Wound infection
16,273 ± 18,712
19,500 ± 26,536
0.002
ii. Pneumonia
14,444 ± 16,127
17,356 ± 24,631
0.002
iii. Bed days
52,218 ± 47,604
60,269 ± 76,765
0.005
Cost estimates if including nonstatistically significant complications
13,890 ± 13,595
16,303 ± 21,038
0.002
Total estimated costs
(US dollars), Mean ± SD
¼ of costs from main analysis:
iii. Bed days
4x costs from main analysis: