Study Finds Nitrous Oxide Suitable and Harmless for Sickle Cell Disease

A recent study could help sedation dentists treating patients with sickle cell disease, as it suggests nitrous oxide is safe for behavioral management.

By Dr. Mehmood Asghar

Sickle cell disease (SCD) is an inherited red blood cell disorder that is characterized by a mutation in the gene that encodes hemoglobin (Hb) subunit β (HBB) (Kato et al., 2018). It has been approximated that over 300,000 infants are born with SCD disease, a number that is feared to rise to 400,000 by 2050 (Piel et al., 2017).

Pathophysiology of Sickle Cell Disease

Hb is a tetrameric protein that is composed of different globulin subunit combinations. The combination of various proteins controls the composition of multiple globulins and hence, the types of Hb that are expressed during various stages of life – the embryonic, fetal, and adult Hb. HbA, the most abundant adult form of Hb, comprises 2 α- and 2 β-globin subunits. A single nucleotide substitution in the β-globin causes SCD. When this mutated Hb is deoxygenated, it polymerizes and damages the erythrocytes by resulting in the removal of water and cations. This results in abnormal rheological properties of the blood and affects the expression of the adhesion molecules, causing hemolytic anemia. At the same time, these damaged, sickle-shaped erythrocytes carry a higher risk of the occlusion of the blood vessels, thereby causing complications such as ischemic tissue damage and organ failure (Piel et al., 2017).

Sickle Cell Disease Patients Require Frequent Surgical Treatment

SCD affects nearly all the body organs. Hence, SCD patients are referred for surgical treatment more often than those without this disease (Hyder et al., 2013). When these surgical procedures – whether medical or dental – involve unconscious or uncooperative children or are time-consuming, they are often performed under conscious sedation with nitrous oxide (N2O).

Although N2O is routinely used in dentistry for treating behavior management of patients with dental anxiety and has been shown to carry minimal acute or chronic adverse effects, anecdotal concerns exist that by allowing patients to breathe lower oxygen concentrations during conscious sedation, it may cause hypoxia and eventually lead to complications such as vasoocclusion and sickle acute chest syndrome (Hill et al., 2021).

Conscious Sedation for Sickle Cell Disease Patients

Currently, having a concentration of less than 50% N2O (mixed with 50% oxygen) is recommended for SCD patients. However, no scientific data is currently available to prove that using lower oxygen concentrations will cause postoperative surgical complications.

A study (Hill et al., 2021) was conducted by researchers at various departments of the University of Illinois, Chicago, (UIC) to investigate whether low oxygen levels during N2O sedation in SCD patients cause any postoperative complications. This pilot study had two main objectives:

  1. To evaluate blood oxygenation levels during routine dental treatment in pediatric sickle cell disease patients under nitrous oxide sedation.
  2. To assess postoperative complications caused by N2O.

How Was the Study Conducted?

In this clinical study, three-to-15-year-old SCD patients were recruited who had visited the graduate pediatric dental clinic at the UIC College of Dentistry. The eligibility criteria included:

  • Patients requiring restorative dental treatment under N2O sedation.
  • Patients who had received medical clearance from their hematologist for the use of N2O.
  • Patients who did not require a preoperative blood transfusion.
  • Patients who presented with a baseline oxygen percentage of 95 or higher.
  • Patients or their legal guardian who could read and comprehend Spanish or English.

A total of 23 patients were included in the study. Before the restorative procedure the subjects received 100% oxygen for 5 minutes, and then titrated a 50:50 mixture of oxygen and N2O. This concentration was maintained throughout the procedure, and the oxygen saturation levels were checked every 10 minutes. After the completion of the procedure, the subjects again received 100% oxygen for 5 min before being discharged. Oxygen saturation levels were also recorded postoperatively. The principal investigator then called each subject 1-3 days after the surgery to inquire about post-surgical complications.

The Findings

The study revealed very interesting findings. While 48% of the subjects received a 50:50 ratio of oxygen and N2O, the remaining received an N2O concentration varying between 30 and 45%. Despite this, the mean oxygen saturation levels in the subjects, both peri and postoperatively, were 99%. A statistically significant difference was also shown between the baseline, perioperative, and postoperative oxygen saturation levels (Table 1).

Table 1 Results of Parried T-test Comparing Oxygen Saturation Levels at Different Timepoints


Interestingly, the mean oxygen saturation levels in the subjects were higher postoperative than at baseline or during the procedure. At the same time, it was observed that 60.9% of subjects exhibited a positive behavioral response, followed by 30.4% with positive, and only 8.7% with a negative response, measured using the Frankl’s Scale (Riba et al., 2017). Furthermore, none of the subjects or caregivers reported any post-surgical adverse effects.

The Conclusion

This study has debunked the myth that N2O sedation in SCD patients can cause complications. The current study highlights that N2O sedation is safe for behavioral management in CSD patients, as it helps them relax and become more cooperative during treatment. Finally, it has been established that N2O sedation does not cause any immediate adverse effects. However, long-term complications or negative effects of N2O conscious sedation still need to be investigated. The findings of this study will help dentists effectively manage SCD patients without fears of complications.


  • Hill, B., da Fonseca, M. A., & Hsu, L. L. (2021). Nitrous oxide for dental procedures in pediatric patients with sickle cell disease: A pilot study. Pediatric Dentistry, 43(6), 481-483.
  • Hyder, O., Yaster, M., Bateman, B. T., & Firth, P. G. (2013). Surgical procedures and outcomes among children with sickle cell disease. Anesthesia & Analgesia, 117(5), 1192-1196.
  • Kato, G. J., Piel, F. B., Reid, C. D., Gaston, M. H., Ohene-Frempong, K., Krishnamurti, L., Smith, W. R., Panepinto, J. A., Weatherall, D. J., Costa, F. F., & Vichinsky, E. P. (2018). Sickle cell disease. Nature Reviews Disease Primers, 4(1), 18010.
  • Piel, F. B., Steinberg, M. H., & Rees, D. C. (2017). Sickle cell disease. New England Journal of Medicine, 376(16), 1561-1573.
  • Riba, H., Al-Zahrani, S., Al-Buqmi, N., & Al-Jundi, A. (2017). A review of behavior evaluation scales in pediatric dentistry and suggested modification to the frankl scale. EC Dent Sci, 16(6), 269-275.


Author: Dr. Mehmood Asghar is a dentist by profession and an Assistant Professor of Dental Biomaterials at the National University of Medical Sciences, Pakistan. Dr. Asghar received his undergraduate and postgraduate dental qualifications from the National University of Science and Technology (NUST). He is also currently pursuing a Ph.D. in Restorative Dentistry from Malaysia. Apart from his hectic clinical and research activities, Dr. Asghar likes to write evidence-based, informative articles for dental professionals and patients. Dr. Asghar has published several articles in international, peer-reviewed journals.

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