Ventilation with Nitrous Oxide During Open Cholecystectomy Increases the Incidence of Postoperative Hypoxemia

Mohammad Maroof, FFARCS, Rashid M. Khan, MD, and Mahmood Siddique, MD

Department of Anesthesiology, King Fahad National Guard Hospital, Kingdom of Saudi Arabia

The effect of intraoperative use of air versus nitrous oxide (N,O) on postoperative oxygen (0,)saturation in blood was evaluated in 40 ASA Class I and I1 patients undergoing elective, open cholecystectomy. Patients were allocated randomly to two groups on the basis of whether they received air (Group At = 20) Or N2 = 20) intraoperatively. Oxygen (Group was recorded on arrival of the patients in the ward, 24 h, and 48 h postoperatively. Although mean O2
Bg

saturation did not differ significantly ( P > 0.05) between the groups Over the first 24 h postoperatively, it was significantly higher ( p < 0.05) in Group A as cornpared to Group 48 ki postoperatively. Incidence Of hypoxemia (0,saturation <90%) was 40% in Group B as compared to 0% in Group A at the end o f 48 h postoperatively. We conclude that the use of N 2 0 during cholecystectomy is associated with a higher incidence
of hypoxemia postoperative~y~

(Anesth Analg 1993;76:10914)

everal groups have shown that general anesthesia for upper abdominal surgery is often followed by a decrease in oxygen (02) saturation that may continue into the late postoperative period (1-3). Whether nitrous oxide (N20) administration during anesthesia plays a role in this phenomenon seems to be controversial. Gawley and Dundee (4) found an association between N20administration and postoperative hypoxemia. However, Web and Nun (5) and Lampe et al. (6) found no such correlative evidence. The aim of the present study was to observe the effect of intraoperative use of N 2 0 versus air in relation to postoperative O2 saturation keeping near constant all other variables such as age, premedication, type of surgery, anesthetic technique, and postoperative analgesia.

Methods
After approval by the Institutional Research Committee, 40 ASA Class I and I1 patients scheduled for elective, open cholecystectomy were selected for this study.
Accepted for publication December 30, 1992. Address correspondence and reprint requests to Dr. Mohammad Maroof, Chairman, Department of Anesthesiology, King Fahad National Guard Hospital, P.O. Box 22490, Riyadh 11426, Kingdom of Saudi Arabia.
01993 by the International Anesthesia Research Society 0003-2999/93/$5.00

Care was taken to exclude patients with history of cardiorespiratory disease. These patients were divided randomly into two groups of 20 patients each on the basis of whether they received intraoperative air and O2(Group A) or N 2 0 and O2(Group B). All patients received a standard general anesthetic technique except for inclusion of N 2 0 or air as per study protocol. The attending anesthesiologist was aware of the group assignment. Premedication consisted of meperidine (1mg/kg) and promethazine (0.5 mg / kg) intramuscularly 1 h before surgery.Anesthesia was induced with a sleep dose of thiopental and fentanyl(1 &kg) and maintained with isoflurane (1-276) with air and 0 2 ( F I o 0.35) ~ or N 2 0 and O2 (F102 0.35). Atracurium was used as the muscle relaxant. Intraoperative heart rate and arterial blood pressure were maintained within 15% of preoperative value by the use of fentanyl and isoflurane (1-2%) that was controlled by the attending anesthesiologist, not by study protocol. Ventilation was controlled. Tidal volume was 10 mL/kg and the respiratory rate was adjusted to maintain an end tidal carbon dioxide at approximately 33-36 mm Hg. At the conclusion of the surgery, the residual neuromuscular block was reversed by a combination of neostigmine and glycopyrrolate intravenously, the dose having been determined after evaluation by analysis of the train-of-four ratio. The patients subsequently were transferred to the postanesthetic care unit where they breathed O2 by face mask
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Table 1. Demographic Characteristics

Sex

Group
A, air B, N20

Age (yr)
37.8 9.15 38.55 8.73

Weight (kg)
73.5 15.15 71.75 r 8.31

Hemoglobin (gm %)
13.0 f 1.02 12.90 0.91

Ma1e:Female (No. patients)

4:16 6:14

* *

Results are expressed as mean + SD, except in last column.

(5 L/min) for 30-45 min after having recorded the initial O2saturation while breathing room air. Postoperative pain was relieved with a combination of meperidine (1 mg/kg) and promethazine (0.25 mg/ kg) administered intramuscularly as required. Postoperative O2saturation was monitored by pulse oximetry (OHMEDA BIOX 3700) and recorded by an anesthesiologist blind to the group assignment. The same oximeter and probe were used in all patients at all time intervals during the study period to avoid errors between different pulse oximeters. O2saturation <90% was interpreted as hypoxemia in this study. O2saturation was recorded as the patient arrived in the ward from the recovery room and subsequently at 24 and 48 h postoperatively. All patients breathed unhumidified room air in the ward. Mean O2saturation values within the two anesthetic groups were analyzed by using paired t-test. The unpaired t-test was used for comparing intergroup data, (demographic data, duration of surgery, dose of narcotics, and O2saturation). Incidence of hypoxemia was analyzed by the test. Values in tables have been expressed as mean ? SD.

Table 2. Duration of Surgery and Perioperative Use of Narcotics

Duration of

surgery
Group A, air B, N20

Intraoperative fentanyl

(min)

(I%)

Postoperative meperidine (mg)

104.20 * 19.68 154.50 52.51* 325.17 25.20 112.20 23.79 117.25 28.16 330.35 41.07

* *

Results are expressed as mean * P < 0.05.

* SD.

Discussion
Several factors have been considered responsible for the pathogenesis of postoperative hypoxemia. Early postoperative hypoxemia is caused by a combination of reduced functional residual capacity resulting from anesthesia and surgery, development of atelectasis (71, and the respiratory depressant effect of anesthesia and opioid analgesia (2). Similarly, many factors may contribute to late hypoxemia, such as an increase in alveolar-arterial Po2difference secondary to persistent reduction in functional residual capacity (8) and alteration in the relationship of closing volume to functional residual capacity (9). Additional factors, such as impaired diaphragm function (lo), splinting of ventilation by abdominal distension, and pain (11) leading to aggravation in peripheral atelectasis, may add substantially to postoperative hypoxemia. By specially designing this study, we were able to keep all of the above variables plus the duration of surgery and postoperative narcotics near constant in the two groups. This enabled us to show a direct cause-and-effect relationship between the use of N 2 0 or air and postoperative O2 saturation. Our study demonstrated that the intraoperative use of N 2 0 for cholecystectomy was associated with a higher incidence of postoperative hypoxemia (40%). By contrast, the use of air in place of N 2 0 led to better preservation of postoperative O2 saturation as indicated by the fact that there was only a 10% and 0% incidence of hypoxemia in this group at 24 and 48 h, respectively. Furthermore, the degree of postoperative O2 saturation continued to improve for the first 48 h in patients receiving air intraoperatively. This was despite the use of a significantly higher dose of intraoperative fentanyl in Group A to provide satisfactory analgesia in lieu of N20. In contrast, patients receiving

Results
The demographic characteristics of the two groups were not significantly different (Table 1). The duration of surgery was nearly identical in the two groups ( P > 0.05). The dose of intraoperative fentanyl was significantly larger in Group A as compared to Group B, but there was no significant difference in the dose of postoperative meperidine administered during 48 h to patients of either group (Table 2). The incidence of postoperative hypoxemia was nearly similar between the groups on arrival in the ward from postanesthetic care unit. However, by the end of 48 h there were 40%hypoxic patients in Group B as compared to none in Group A (Table 3). Similarly, there was a statistically insignificant ( P > 0.05) difference in the mean O2saturation between the groups during the first 24 h, but a marked improvement was observed at the end of 48 h in Group A. By contrast, in Group B patients, mean 0 2 saturation continued to deteriorate for the first 48 h. The difference in mean O2 saturation between the groups was significant ( P < 0.05) at 48 h (Table 4).

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Table 3. Incidence of Postoperative Hypoxemia in Two Groups at Different Time Interval

Postoperative Hypoxemia (0, saturation ~ 9 0 % ) At arrival in the ward, Group A, air B, N20
'P < 0.05.

End of first 24 h No. patients

(10) (15) 2* 8* (10) (40)

End of first 48 h No. Patients 0 8*

(0) (40)

No. patients

2
3

Table 4. Mean O2 Saturation Characteristics Within First 48 H after Anesthesia Preoperative O2 saturation Group
(%)

Postoperative O2 saturation (%) At arrival in the ward

93.30 f 3.76* 92.35 f 2.27*

End of first 24 h
93.95 k 3.12* 92.05 f 4.22

End of first 48 h
95.10 k 1.77 91.35 k 4.68*t

97.15 f 1.46 97.00 f 1.68

Results are expressed as mean ? SD. P < 0.05 within group (paired 1-test). t P < 0.05 compared in between the group (unpaired 1-test).

intraoperative N 2 0 showed gradual deterioration in postoperative O2 saturation during the study period. The difference in the mean O2saturation between the two groups was most marked at the end of the first 48 h. None of the patients in our series developed clinical evidence of frank atelectasis or pneumonia that would necessitate chest radiograph or magnetic resonance imaging postoperatively. That there is no significant difference in the 0 2 saturation between the groups of patients on arrival in the ward probably reflects the predominant action of the residual anesthetics. However, the role of absorption atelectasis in Group B patients may be observed, even at this time interval, as a lower mean O2 saturation, although insignificant when compared to Group A patients. Lampe et al. (6) have reported near identical incidence of hypoxemia (02 saturation 4 6 % ) within the first 24 h after anesthesia in patients receiving intraHowever, the same group operative N 2 0 or 100% 02. of workers covering >2 postoperative days of O2 saturation monitoring have documented a higher incidence of hypoxemia in patients receiving intraoperative N 2 0 when compared to those receiving 100% 0 2 (21% versus 15%, respectively). The findings of this study show a higher incidence of hypoxemia in the N 2 0 group reported by Eger I1 et al. (12) although the difference remains statistically insignificant. The findings of our study are not in total agreement with those of Lampe et al. (6) or Eger I1 et al. (12) mainly because in their study patients undergoing nonabdominal surgery (and hence less prone to hypoxemia) were selected and 100%O2was used in the control group as opposed

to air used in our study. We believe that nitrogen or air provides greater protection against absorption atelectasis than does 100%O2and thereby lessens hypoxemia. Furthermore, Lampe et al. (6) and Eger I1 et al. (12) have defined hypoxemia as O2saturation <86% as opposed to our criteria of <90%. In our series, we had only 1 (5%) and 2 (10%) hypoxemic patients with O2 saturation 4 6 % at 24 and 48 h, respectively, in Group B as compared to none in Group A. It is, therefore, apparent that with this definition of hypoxemia (0, saturation <86%) our results are only slightly different from the results of Eger I1 et al. (12). We believe that there is no single factor that is responsible for the increased incidence of postoperative hypoxemia after N 2 0 administration. A delicate interplay of the several factors may be responsible. First, there is a greater risk of absorption atelectasis when N 2 0 is used with O2because of the substantial affinity of hemoglobin for O2and the continuous metabolic utilization of 02. In contrast, when air is used with 0 2 , the low solubility of nitrogen provides greater protection against the absorption atelectasis than does N20, and hence there is better preservation of postoperative O2 saturation. Secondly, N 2 0 is known to depress ciliary function (13). Thirdly, N 2 0 may increase bronchial secretions (14). The overall effect of the second and third factor in conjunction with that produced by isoflurane could be the retention of mucus and subsequent microatelectasis over and above that produced by the first factor. All this may lead to significant atelectasis and may contribute to postoperative hypoxemia. Therefore, we conclude that air and O2 with suitable combination of inhaled anesthetic and

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short-acting narcotics for maintenance of anesthesia may be more appropriate in reducing the degree and duration of postoperative hypoxemia in patients undergoing open cholecystectomy.
We are most grateful to Miss Nerissa Monte Nico for secretarial help in this manuscript.

References
1. Knudsen J. Duration of hypoxaemia after uncomplicated upper abdominal and thoracoabdominal operations. Anaesthesia 1970; 25:372-5. 2. Jones JG, Sapsford DJ, Wheatley RG. Postoperative hypoxaemia: mechanisms and time course. Anaesthesia 1990;45:566-73. hy3. Reeder MK, Goldman MD, Loh L, et al, ~~~~~~~~~~i~~

poxaemia after major abdominal vascular surgery. Br J Anaesth 1992;68:23-6. 4. cawley TH, Dundee JW, Attempts to reduce respiratory plications following upper abdominal operations. Br J Anaesth 1981;531073-8. 5. Web SJS, Nunn JF. A comparison between the effect of nitrous oxide and nitrogen on arterial Po*. Anaesthesia 1967;22:69-80.

6. Lampe GH, Wauk LZ, Whitendale P, et al. Postoperative hypoxemia after nonabdominal surgery. A frequent event not caused by nitrous oxide. Anesth Analg 1990;71:597-601. 7. Hedenstiema G. Gas exchange during anaesthesia. Br J Anaesth 1990;64:507-14. 8. Meyers JR, Lembeck L, OKane H, Baue AE. Changes in functional residual capacity of the lung after operation. Arch Surg 1975;110:576-83. 9. Alexander JI, Spence AA, Parikh RK, Stuart B. The role of airway closure in postoperative hypoxaemia. Br J Anaesth 1973;45: 36-60. 10. Ford GT, Whitelaw WA, Rosenal TW, et al. Diaphragm function after upper abdominal surgery in humans. Am Rev Resp Dis 1983;127:431-6. 11. Atkinson s, Rushman GB,L~~JA. Accidents, comp~ications and sequelae of anaesthesia. In: A synopsis of anaesthesia. Bombay: KM Varghese Company, 1987321-2. 12. Eger 11 EL L a m p GH, Wauk LZ, et al. Clinical pharmacology of nitrous oxide: an argument for its continued use. Anesth Analg 1990;71:575-85. 13. Forbes AR, Horrigan RW. Mucociliary flow in the trachea during anesthesia with enflurane, ether, nitrous oxide and morphine. Anesthesiology 1977;46:319-21. 14. Smith WDA. Pharmacology of nitrous oxide. Int Anesthesiol Clin 1971;9:91-123.