Ain-Shams Journal of Anaesthesiology

ORIGINAL ARTICLE
Year
: 2016  |  Volume : 9  |  Issue : 1  |  Page : 99--103

Effect of nitrous oxide inhalation on induction dose of propofol, induction time, oxygen saturation, and hemodynamic responses to laryngoscopy and intubation


Rajan Sunil, Sarath Vijayakrishna Pillai, Kumar Lakshmi 
 Department of Anaesthesiology and Critical Care, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India

Correspondence Address:
Rajan Sunil
Department of Anaesthesiology and Critical Care, Amrita Institute of Medical Sciences, Kochi, Kerala, 682 041
India

Abstract

Context Nitrous oxide enhances the anesthetic potential of other agents and thereby reduces their requirement. Aims This study aimed to determine the effect of nitrous oxide inhalation on the induction dose of propofol, induction time, oxygen saturation, and hemodynamic responses to laryngoscopy and intubation. Settings and design This was a randomized, prospective clinical trial. Participants and methods A total of 150 surgical patients ASA status I and II were included in the study. Patients in group A inhaled 66% nitrous oxide in oxygen for 3 min, whereas in group B, 100% oxygen was used. In both the groups, patients were administered a propofol bolus 20 mg every minute intravenously after 3 min of gas inhalation until induction was achieved. Loss of response to verbal command and no response to jaw thrust were considered the endpoint of induction. Patients were then intubated after administration of suxamethonium 2 mg/kg. Results The mean dose of propofol required for induction was significantly lower in group A compared with group B (30.4 ± 26.17 vs. 101.87 ± 26.19), as was the induction time (1.52 ± 1.31 vs. 5.09 ± 1.33). Heart rate was comparable throughout the study period. At induction, group A had a significantly higher mean arterial pressure (MAP) (94.51 ± 16.21 vs. 86.57 ± 15.47). At 5 and 10 min, MAP was significantly high in group B and significantly high oxygen saturation was observed at induction (99.81 ± 0.46 vs. 99.96 ± 0.26). No patient developed desaturation (SpO 2 <90%) during the study. Conclusion Inhalation of 66% nitrous oxide for 3 min significantly reduced the induction time and the dose of propofol, prevented a precipitous decrease in MAP at induction, and effectively attenuated stress response to laryngoscopy and intubation without desaturation.



How to cite this article:
Sunil R, Pillai SV, Lakshmi K. Effect of nitrous oxide inhalation on induction dose of propofol, induction time, oxygen saturation, and hemodynamic responses to laryngoscopy and intubation.Ain-Shams J Anaesthesiol 2016;9:99-103


How to cite this URL:
Sunil R, Pillai SV, Lakshmi K. Effect of nitrous oxide inhalation on induction dose of propofol, induction time, oxygen saturation, and hemodynamic responses to laryngoscopy and intubation. Ain-Shams J Anaesthesiol [serial online] 2016 [cited 2019 Jul 21 ];9:99-103
Available from: http://www.asja.eg.net/text.asp?2016/9/1/99/178887


Full Text

 Introduction



Nitrous oxide, the time-tested anesthetic gas, is used commonly as an adjuvant analgesic and as a vehicle for the administration of more potent volatile agents. It enhances the anesthetic potential of other agents and thereby reduces their requirement [1] .

The primary objective of this study was to determine whether the induction dose of propofol could be reduced when nitrous oxide was administered before intravenous induction. The secondary objectives included assessment of induction time, oxygen saturation, and hemodynamic response to laryngoscopy and intubation.

 Participants and methods



This study was carried out at the Amrita Institute of Medical Sciences and Research Centre, Kochi, Kerala, India, during the period September 2012 to September 2014. On the basis of the results obtained on the dose of propofol and induction time from the earlier publications [2] and with 99% confidence and 99% power, the minimum sample size came to 19 in each group. Therefore, after obtaining Institutional Ethical Committee clearance, we recruited 150 consenting patients in this randomized, prospective clinical trial. The study population included patients undergoing surgery under general anesthesia with endotracheal intubation, aged 20-50 years, ASA physical status I and II.

Patients were divided randomly into two equal groups using the closed-envelope technique: group A and group B. Patients in group A received incremental doses of propofol following nitrous oxide inhalation for 3 min and patients in group B received only propofol as an induction agent.

Patients belonging to ASA III and above and pregnant patients and those with obesity, chronic obstructive pulmonary disease, bronchial asthma, interstitial lung diseases, and uncontrolled hypertension were excluded from the study.

Both the groups were kept nil per os, 8 h for solids and 2 h for clear fluids. All patients received ranitidine 150 mg, metoclopramide 10 mg, and alprazolam 0.5 mg orally on the night before surgery. Ranitidine 150 mg and metoclopramide 10 mg were repeated with a sip of water on the day of surgery. In the theater, a large bore intravenous access was started under local anesthesia and patients were premedicated with intravenous glycopyrrolate 0.2 mg and intravenous fetanyl 2 μg/kg.

Patients in group A were asked to inhale 4 l/min nitrous oxide and 2 l/min of oxygen, whereas patients in group B were preoxygenated with 6 l/min of oxygen for 3 min with a tight-fitting face mask. Loss of response to verbal command (taking deep breaths/opening eyes) and no response to jaw thrust were considered the endpoint of induction.

Starting at the end of 3 min, after assessing response to verbal command and jaw thrust, both groups were administered a propofol bolus 20 mg every minute intravenously. Induction time was calculated as the time from the start of propofol injection to loss of response to verbal command and jaw thrust, and induction dose as the total amount of propofol administered till that time.

After confirming the ability to mask ventilate, patients were administered suxamethonium 2 mg/kg and midazolam 1 mg intravenously and ventilated with the same gas mixture plus isoflurane 1%. After 1 min, a quick and gentle laryngoscopy was performed and patients were intubated with an appropriate-sized endotracheal tube.

Heart rate, systolic blood pressure, diastolic blood pressure, and mean arterial pressure (MAP) of each patient were measured at preinduction, at induction, and 1, 3, 5, 10, and 15 min after induction. Desaturation was defined as SpO 2 less than 90% and if any patient developed desaturation during nitrous oxide inhalation, the patient was ventilated with 100% oxygen and the data were not used for statistical analysis.

Statistical analysis

Data were analyzed using IBM SPSS statistics 20 software (Bengaluru, India). To compare the averages of continuous variables following a normal distribution, an independent-sample t-test was used and for those not following a normal distribution, the Mann-Whitney U-test was used. Paired-sample t-test was used to compare the average parameters and the χ2 -test was used for categorical variables. Level of significance was considered at P value less than 0.05.

 Results



Distribution of age, sex, height, weight, and ASA grading of the patients in both groups were comparable.

The mean dose of propofol required for induction was significantly lower in group A compared with group B (30.4 ± 26.17 vs. 101.87 ± 26.19, [Table 1], [Figure 1]. Similarly, the induction time was also significantly shorter in group A (1.52 ± 1.31 vs. 5.09 ± 1.33, [Table 2], [Figure 2].{Figure 1}{Figure 2}{Table 1}{Table 2}

Heart rate in both groups at preinduction as well as throughout the study period were comparable (P < 0.05, [Table 3], [Figure 3]. Preinduction MAP was comparable between groups, but at induction, group A had a significantly higher MAP (94.51 ± 16.21 vs. 86.57 ± 15.47, P = 0.002). However, MAP values were significantly higher in group B at 5 min (83.09 ± 12.935 vs. 88.42 ± 14.600, P = 0.019) and 10 min (82.12 ± 12.013 vs. 87.21 ± 13.225, P = 0.014), [Table 4], [Figure 4].{Figure 3}{Figure 4}{Table 3}{Table 4}

Preinduction oxygen saturation was comparable between groups. Statistically, there was a significant difference at induction, with group B showing a higher value (99.81 ± 0.46 vs. 99.96 ± 0.26, P = 0.887). Thereafter, it was comparable in both groups [Table 5], [Figure 5]. No patient developed desaturation (SpO 2 <90%) during the study.a{Figure 5}{Table 5}

 Discussion



The essential components of anesthesia include immobility, unconsciousness, and suppression of autonomic responses. This can be achieved with the judicious use of multiple drugs, which include inhaled and intravenous agents. Use of a single drug to provide adequate depth of anesthesia could be dangerous as higher doses may be required with an increased risk of side effects. Thus, combinations of drugs that potentiate the anesthetic effects will enable the usage of fewer drugs, which will subsequently reduce complications. It has been documented that when used in conjunction, nitrous oxide decreases the requirement of intravenous anesthetic agents such as thiopentone and propofol [2],[3],[4] .

Although in the west, there are moves to omit routine use of nitrous oxide [5],[6] , it still remains the most commonly used inhalation agent in developing countries. The future of nitrous oxide does not seem to be bleak, mainly because of its cost effectiveness [7] . The available alternative, xenon, seems to be more potent than nitrous oxide and requires only a minimal supplement of a hypnotic anesthetic to suppress noxious stimulation [8] . However, because of the high cost, xenon is an unlikely replacement for nitrous oxide in the near future.

Nowadays, propofol has become the most commonly used agent for induction of anesthesia [9] . It is a costlier drug compared with the older induction agents and an additional financial burden occurs as unused drug is thrown away in partially full syringes because of its recommended expiration of 6 h once opened [10] . Thus, the patients end up paying more than what they have actually consumed. As economy of treatment is a growing concern in the health sector nowadays, the observation in our study that inhalation of nitrous oxide for 3 min leads to a 70% reduction in the induction dose of propofol should be paid attention.

Hypotension is invariably associated with propofol induction [11] , more so in elderly individuals [12] . Preloading with colloid [13] or crystalloids [14] is not very effective in preventing this hypotension, whereas combining propofol with ketamine [15],[16] or etomidate [16] may prevent hypotension. Conflicting results have been found on the effectiveness of ephedrine in this respect [13],[14],[15],[17],[18],[19] . However, this drawback of propofol induction could be overcome to a huge extent by 3 min of nitrous oxide inhalation, as observed in our study, as hypotension at loss of verbal response was comparatively less.

Whether a reduction in the induction dose of propofol could lead to an exaggerated stress response to laryngoscopy and intubation would be a natural concern. It was found that nitrous oxide inhalation effectively suppressed the heart rate as well as the hypertensive responses, at the same time maintaining MAP at induction.

Another concern while adopting this technique could be desaturation. No desaturation was observed at induction and saturations in both groups remained well within clinically acceptable limits (99.81 ± 0.46 vs. 99.96 ± 0.26). Thus, if patients are chosen carefully, avoiding those with anticipated difficult airway and low cardiorespiratory reserve, the technique seems to be quite safe in experienced hands.

 Conclusion



Inhaling 66% nitrous oxide for 3 min significantly reduced the induction dose of propofol. In addition, this technique reduced induction time, prevented a precipitous decrease in MAP at induction, and effectively attenuated stress response to laryngoscopy and intubation without desaturation.

 Acknowledgements



Conflicts of interest

There are no conflicts of interest.

References

1Becker DE, Morton Rosenberg M. Nitrous oxide and the inhalation anesthetics. Anesth Prog 2008; 55:124-131.
2Ng JM, Hwang NC. Inhaling nitrous oxide reduces the induction dose requirements of propofol. Anesth Analg 2000; 90:1213-1216.
3Dominguez VC, Bellolio PC. Iinfluence of inhaled nitrous oxide on the induction doses of propofol and thiopental assessed by auditary evoked potentials. Anestesiol Reanim 2007; 54:475-479.
4Stuart PC, Stott SM, Millar A, Kenny GN, Russell D. Cp50 of propofol with and without nitrous oxide 67%. Br J Anaesth 2000; 84:638-639.
5Enlund M, Edmark L, Revenäs B. Ceasing routine use of nitrous oxide - a follow up. Br J Anaesth 2003; 90:686-688.
6L Dimpel, M Enlund. Use of nitrous oxide in anaesthesia. Br J Anaesth 2003; 91:605-606.
7Lyratzopoulos G, Blain KM. Inhalation sedation with nitrous oxide as an alternative to dental general anaesthesia for children. J Public Health Med 2003; 25:303-312.
8Barakat AR, Schreiber MN, Flaschar J, Georgieff M, Schraag S. The effective concentration 50 (EC50) for propofol with 70% xenon versus 70% nitrous oxide. Anesth Analg 2008; 106:823-829.
9Stoelting RK, Hillier SC, editors. Pharmacology and Physiology in Anaesthetic Practice. 4th ed. Philadelphia: Lippincott Williams and Wilkins; 2006. Nonbarbiturate ntravenous anaesthetic drugs; p. 155-178.
10Gillerman R, Browning R. Drug use inefficiency: a hidden source of wasted health care dollars. Anesth Anal 2000; 91:921-924.
11Miner JR, Burton JH Clinical practice advisory: emergency department procedural sedation with propofol. Ann Emerg Med 2007; 50:182-187.
12Reich DL, Hossain S, Krol M, Baez B, Patel P, Bernstein A, Bodian CA. Predictors of hypotension after induction of general anesthesia. Anesth Analg 2005; 101:622-628.
13Dhungana Y, Bhattarai BK, Bhadani UK, Biswas BK, Tripathi M. Prevention of hypotension during propofol induction: a comparison of preloading with 3.5% polymers of degraded gelatin (Haemaccel) and intravenous ephedrine. Nepal Med Coll J 2008; 10:16-19.
14M Kumar, N Saxena, AK Saxena. The effect of a colloid or crystalloid preload on hypotension caused by induction of anaesthesia with propofol and fentanyl. J Anaesth Clin Pharmacol 2008; 24:409-412.
15Dutta V, Ahmad M, Gurcoo S, Ommid M, Qazi MS. Prevention of hypotension during induction of anesthesia with propofol and fentanyl: comparison of preloading with crystalloid and intravenous ephedrine. IOSRJDMS 2012;1:26-30
16Ozkoçak I, Altunkaya H, Ozer Y, Ayoðlu H, Demirel CB, Ciçek E. Comparison of ephedrine and ketamine in prevention of injection pain and hypotension due to propofol nduction. Eur J Anaesthesiol 2005; 22:44-48.
17Hosseinzadeh H, Eidy M, Golzari SEJ, Vasebi M. Hemodynamic stability during induction of anesthesia in elderly patients: propofol+ketamine versus propofol+etomidate. J Cardiovasc Thorac Res, 2013; 5:51-54.
18Ayatollahi V, Behdad S, Kargar S, Yavari T. Comparison of effects of ephedrine, lidocaine and ketamine with placebo on injection pain, hypotension and bradycardia due to propofol injection: a randomized placebo controlled clinical trial. Acta Med Iran 2012; 50:609-614.
19El-Tahan MR. Preoperative ephedrine counters hypotension with propofol anesthesia during valve surgery: a dose dependent study. Ann Card Anaesth 2011; 14:30-40.