Second Gas Effect and * - Oakland University

Report
Nitrous Oxide and the
Second Gas Effect on
Emergence from
Anesthesia
Molly Orr, BS, BSN, CCRN, SRNA
Oakland University-Beaumont
Graduate Program of Nurse Anesthesia
Peyton, P. J., Chao, I., Weinberg, L., Robinson, G. J. B., &
Thompson, B. R. (2011). Nitrous oxide and the second gas
effect on emergence from anesthesia. Anesthesiology,
114(3), 596-602.
 Departments of Anesthesia and Surgery, Austin Hospital,
Melbourne, Australia
 Department of Surgery, University of Melbourne,
Melbourne, Australia
Definition
 What is second gas effect?
 What do we know about it?
 Why is it important?
Study concept
 Does the elimination of N2O affect the rate of decrease
in end-tidal and arterial sevoflurane concentrations
(…and thus speed emergence)?
 The null hypothesis: The rapid diffusion of N2O at the
end of inhalational anesthesia has no effect on the rate
of reduction in end-tidal and arterial concentrations of
volatile anesthetic (i.e. sevoflurane)
Study design
 Randomized controlled study
 Patients randomly assigned to experimental or control
group via sealed envelope (N=20)
 Control group (n=10): Gas mixture of sevo in air-oxygen
 Experimental (nitrous oxide) group (n=10): Gas mixture
of sevo in a 2:1 mixture of nitrous oxide-oxygen
Inclusion criteria
 Adults (> 18 yo) capable of giving informed consent
 General surgery at least 1 hour duration
 Requires arterial line for hemodynamic monitoring
 Arterial line samples used for gas analysis
Exclusion criteria
 History of severe lung disease (PFT criteria)
 Symptomatic ischemic heart disease
 Super obesity (BMI>45)
 Pregnancy
 H/O severe PONV
 Critically ill/immunologically compromised
 Vit B12 or folate deficiency
 Presence of gas-filled, space occupying lesion
Methods used
 Premed: 1-2 mg midazolam IV
 Standard monitoring + arterial line + BIS
 Preoxygenated
 Induction: 1.5-2.5 mg/kg propofol IV, opioids (1-2 mcg/kg
fentanyl and/or morphine 0.05-0.1 mg/kg), nondepolarizing
neuromuscular blocker
 Endotracheal intubation, controlled ventilation 12-15
breaths/min, EtCO2 maintained 28-33 mmHg
 Maintenance: Inhalational anesthetic mixture (with airoxygen or with nitrous-oxygen) initiated and sevo
concentration adjusted to maintain BIS 40-60 (N2O does
not affect BIS!)
 Normothermia with forced air warming device
Methods cont’d
At conclusion of surgery:
 Baseline 10 mL arterial blood sample + 1 mL sample for
respiratory blood gas analysis
 End-tidal gas concentrations over 20 sec recorded
simultaneously with gas analyzer
 Baseline hemodynamic, ventilation data, SpO2, temp and
BIS numbers recorded
 After baseline obtained, neuromuscular blockade reversed
with 2.5 mg neostigmine and 0.4 mg glycopyrrolate, fresh
gas mixture changed to 100% O2 at 9 L/min
Methods cont’d
 Arterial blood gas samples drawn, end-tidal gas analysis,
and other vital data collected at 2 min and 5 min
 Patient then loudly commanded to open his or her eyes,
command repeated every 30 sec until response; time
from command until eye opening was noted
 Extubation after standard criteria met; time to
extubation noted
 Final arterial blood gas sample obtained in PACU at 30
min
The dependent variables: Primary
and Secondary Endpoints
 “Primary study endpoints”:
 Differences in the fraction of baseline partial pressures of
sevoflurane in arterial blood at 2 min and 5 min
 End-tidal sevo partial pressures at 2 min and 5 min
 End-tidal and arterial concentrations of CO2 were also
determined at 2 min and 5 min
 “Secondary study endpoints”:
 BIS number comparisons between the two groups at 2, 5,
and 10 min
 Time to eye opening
 Time to extubation
Statistical Analysis
 Estimated 20 patients required for analysis
 Two-tailed t test for unpaired data (with Bonferroni
correction for multiple measurements in each patient)
 Two-way ANOVA to determine whether any measured
differences changed significantly over time
 Best-fit curves for primary endpoints were generated
using least squares method
 Two-tailed t test used for secondary endpoints (after
Kolmogorov-Smirnov normality testing)
 P value of 0.05 or less considered statistically significant
Results/Conclusion
 During the first 5 min after conclusion of anesthesia, the
arterial partial pressure of sevo was 39% higher in the
control group than in the nitrous oxide group (P<0.04), but
was not found to be statistically significant at 2 min and 30
min
 End-tidal differences in sevo were not significant between
the two groups at 2 min and 5 min
 PaCO2 decline at 2 min was significant in N2O group vs. the
control group (d/t diffusion hypoxia), but no sig diff
remained at 5 min
 No significant diff in BIS at 2 and 5 min between two groups
 Times to eye opening and extubation were significantly
shorter in nitrous oxide group (8 min and 10 min,
respectively) compared to control group (11 min and 13
min). [P<0.04]
Strengths of study
 Independent variables were consistent between the two
groups (e.g. age, sex, weight, operative time, baseline
vent parameters, baseline VS, baseline temps and BIS
numbers)
 Anesthetic technique was standardized between two
groups (apart from administration of nitrous oxide)
 Measurements conducted in identical manner between
two groups
Limitations of study
 Small sample size (N=20, two outliers later excluded)
 Variations in characteristics of people who enrolled in
study (e.g. age, end organ function, smoker vs. nonsmoker, V/Q mismatching, etc.)
 Confounding variables as identified by authors, such as
trend toward lower HR and BP in nitrous oxide group,
which correlates to 10-20% lower cardiac output and
may affect alveolar anesthetic concentrations
 Use of nitrous with volatile anesthetic reduces volatile
anesthetic dose; has “MAC sparing” effect
 No statistical significance was found in end-tidal sevo
(i.e. alveolar) concentrations between the two groups
Overall takeaway
 How can we use this in practice?
 A more rapid emergence?

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