Children with Sickle Cell Anemia Experience Severe Oxygen Desaturation During Night and After Six-Minute Walk Distance Test

Respiratory complications are the first causes of death among adult patients with sickle cell anemia (SCA). Finding risk factors for children is important. We study clinical, biological, respiratory and heart parameters, as well as exercise and sleep oxygen saturation in SCA children.

We conducted a prospective study in homozygous SS or S/beta 0 thalassemic children. A chronic transfusion program was an exclusion criterion. We recorded the number of vaso-occlusive crises (VOC) the year before and after inclusion, past history of acute chest syndrome (ACS), hydroxyurea treatment, tonsils size, baseline heart rate and blood pressure, baseline hemoglobin (Hb), reticulocytes, fetal Hb levels, leukocytes and platelets counts, total bilirubin, aspartate aminotransferase (AST), lactate deshydrogenase (LDH). All patients underwent respiratory function testing (RFT), echocardiography assessing tricuspid regurgitation velocity jet (TRV). We measured daytime oxygen saturation using a Radical Masimo set ® pulse oximeter. All patients underwent a non-encouraged six-minute walk test (6MWT). Nocturnal pulse oximetry was recorded using a Nonin ® device during 3 consecutive nights for 30 patients. We considered the average night-time oxygen saturation and the percentage of sleep time with oxygen saturation less than 90%. Statistical analysis was conducted using the Fisher exact test for categorical variables and the Wilcoxon test for continuous variables.

Forty-two unselected SCA children were enrolled. Three patients were secondarily excluded because the echocardiography revealed asymptomatic cardiac anomalies (two pulmonary valve stenosis and one persistent arterial canal). In the remaining 39 patients, 38 were SS and one was S/beta 0 thalassemic. Median age was 10.8 years (range 5.7–17); 25 patients were females (64%). The median number of VOC was 0 the year before inclusion (range 0–6), and 0 the year after (range 0–7). Fifteen patients (38%) had displayed at least one ACS. Nine patients (23%) were receiving hydroxyurea treatment. Sixteen patients (43%) had tonsillitis enlargement. Median basal heart rate was 97 bpm (range 75–122). Mean systolic blood pressure was 107 ± 11.3 mm Hg and mean diastolic blood pressure was 64 ± 6.6 mm Hg. Mean Hb was 7.9 ± 1.2 g/dL, mean reticulocyte count was 236 ± 82 Giga/L, median HbF was 9.2 % (range 0.8–28), mean leukocyte count was 11.1 ± 3.2 Giga/L, mean platelet count was 407 ± 132 Giga/L. Median total bilirubin, AST, and LDH were, respectively, 41.5 mg/dL (range 13–163), 62 UI/l (range 35–132), and 1421 UI/l (range 618–1893) (normal range for LDH in our lab 125–243). Fifteen patients (38.5%) had abnormal RFT: 4 had obstructive pattern, 3 had restrictive pattern, and 3 had both. Left ventricular diastolic function was normal for all patients. Six patients had a TRV above 2.6 m/s. Median daytime oxygen saturation was 97 % (range 89–100). One patient had a daytime saturation below 92%. Median nocturnal oxygen saturation was 94.7 % (range 87.7–99.5). Ten patients (33%) displayed average night-time saturation below 92%. Eleven patients (37%) spent more than 10% of their sleep time with oxygen saturation below 90%. Mean six-minute walk distance (6MWD) was 547 ± 99 m. After the 6MWT, 14 patients (35%) had an oxygen saturation below 92%. Median difference in oxygen saturation before and after the test was 2% (range −57, +2). Nocturnal hypoxemia was not associated with age, gender, tonsils size, hydroxyurea treatment, past history of ACS, RFT pattern, number of VOC, leukocytes, platelets, LDH, bilirubin nor AST. It was associated with Hb level (7.2±1.2 g/dL if nocturnal hypoxemia vs 8.4±1.1, p=0.02), daytime oxygen saturation (94% [range 92–99] if nocturnal hypoxemia vs 98% [range 89–100], p=0.03), and oxygen saturation after 6MWT (91% [range 40–99] if nocturnal hypoxemia vs 96% [range 79–100], p=0.03). Children with a TRV above 2.6m/s had a significantly lower Hb level (7.4 g/dL [6.4–8.1] vs 8.5 [6.5–10.6]).

Our study emphasizes the frequency of night-time oxygen desaturation in SCA children. It shows that a simple effort can induce a significant decrease in oxygen saturation. The consequences of hypoxemia are difficult to assess given the small sample size. One can hypothesize that hypoxemia and hypoxia/reoxygenation cycles both contribute to the pathophysiology of the disease through inflammation and vascular injury.

No relevant conflicts of interest to declare.