Pulse Oximetry and Factors Associated With Hemoglobin Oxygen by djh75337


									          Pulse Oximetry and Factors Associated With Hemoglobin Oxygen
                 Desaturation in Children With Sickle Cell Disease
           By Wayne R. Rackoff, Nanette Kunkel, Jeffrey H. Silber, Toshio Asakura, and Kwaku Ohene-Frempong

The observation of low transcutaneous arterial oxygen sat-               were not seen in Hb SC patients. During acute illness, Hb
uration (SaO,) in otherwise well sickle cell patients has                SS patients with acute chest syndrome had transcutaneous
lead to questions about the interpretation of pulse oxi-                 SaO, values that were less than 96%and at least 3 points
metry values in these patients. We undertook a prospec-                  lower than measurements made when they were well. A
tive study of children with sickle cell disease to (1) deter-            nomogram was designedto aid in the interpretation of trans-
mine the prevalence of, and factors associated with, low                 cutaneous SaO, in acutely illHb SS patients when a compar-
transcutaneous SaO, in clinically well patients, (2)   develop           ison value is not available. The accuracy of pulse oximetry
an algorithm for the use of pulse oximetry in acutely ill pa-            was shown by the correlation between SaO, measured by
tients, and (3) assess the accuracy of pulse oximetry in                 pulse oximetry and calculated by using the patient’s oxygen
these patients. Eighty-six clinically well children with he-             dissociation curve and PaO, (r = .97). This study provides
moglobin (Hb) SS had a lower mean transcutaneous SaO,                    evidence that Hb oxygen desaturation is not a universalfind-
than 22 Hb SC patients and 10 control subjects (95.6% v                  ing among children with sickle cell disease and identifies
99.1 % v 99.0%, respectively;P < . O O l ) . In Hb SS patients,          factors associated with Hb oxygen desaturation. We con-
a history of acute chest syndrome and age greater than 5                 clude that pulse oximetry may be useful to assess whether
years were associated with lower transcutaneous SaO,                     progressive pulmonary dysfunction begins at an early age in
(mean 93.8% for those with a history of acute chest syn-                 Hb SS patients, and to assess acutely ill patients for the
drome v 97.8% for those without a history of acute chest                 presence of hypoxemia associated with acute chest syn-
syndrome, and 94.0% for patients > 5 years old ~ 9 7 . 2 %  for          drome.
those 5 5 years old; P < ,001). These associations                       0 1993 by The American Society of Hematology.

P    ULSE OXIMETRY is a rapid, noninvasive method for
      measuring arterial hemoglobin (Hb) oxygen satura-
tion. It is reliable in many clinical settings, and performs
                                                                         mal range. Others have found that transcutaneous SaO, val-
                                                                         ues are accurate when compared with Hb oxygen saturation
                                                                         values derived from the right-shifted oxygen dissociation
well despite a variety of patient conditions that were sus-              curves of Hb SS patients and the measured PaO, .’ We, there-
pected of interfering with accurate measurement of transcu-              fore, undertook a prospective study to (1) determine the
taneous arterial Hb oxygen saturation (Sa0,).’-4                         prevalence of, and factors associated with, low transcutane-
   Pulse oximetry is often used in the evaluation of patients            ous SaO, in clinically well sickle cell patients; (2) develop an
with sickle cell disease who are suspected of having acute               algorithm for the use of pulse oximetry in acutely ill sickle
chest syndrome. Hypoxemia is common in children with                     cell patients; and (3) assess the accuracy ofpulse oximetry in
acute chest syndrome, and exchange transfusion is advo-                  patients with sickle cell disease.
cated when the PaO, is less than 70 mm Hg while the patient
                                       Some clinicians have
is breathing supplemental ~ x y g e n . ~                                                 MATERIALS AND METHODS
questioned the accuracy of pulse oximetry in patients with
                                                                            Study population. Patients with Hb SS or Hb SC who were 5 18
sickle cell disea~e,~.’ we have seen a number of patients
                       and                                               years of age were eligible for study. This study was approved by the
without other signs and symptoms of respiratory distress                 Institutional Review Board of The Children’s Hospital of Philadel-
who have transcutaneous SaO, values below the usual nor-                 phia. At the time of enrollment in the study, informed consent was
                                                                         obtained from the patient’s parents and, when appropriate, the pa-
                                                                         tient. Specimens were obtained only at the time of clinically indi-
   From the Divisions QfHematology, Oncology and General Pediat-         cated venipuncture or arterial sampling.
rics, The Children ‘s Hospital of Philadelphiu, and the Department          Patients were enrolled at the time of routine hematology clinic
of Pediatrics, University of Pennsylvania School ofMedicine, Phila-      visits at The Children’s Hospital of Philadelphia between January
delphia.                                                                  15, and September 15, 1991. Twenty-seven percent of Hb SS and
   Submitted June 15, 1992; accepted February 4, 1993.                   23% of Hb SC patients registered in the Comprehensive Sickle Cell
   Supported by Comprehensive Sickle Cell Center Grant No. P60-          Center at The Children’s Hospital of Philadelphia were enrolled in
HL-38632from the National Heart, Lung, and Blood Institute, Na-          this part ofthe study. The ratio of Hb SS to Hb SC patients enrolled
tional Institutes of Health. J.H.S. is supported by Grant No. K04-       in the study was not significantly different from the patient popula-
CA-01480fiom the National Cancer Institute, National Institutes of       tion of the center ( P = .66). Patients’ resting pulse oximetry values
Health. Nellcor, Inc provided a pulse oximeter on loan for use dur-      and medical history. including major complications of sickle cell
ing this study, but had no part in the design, execution, or reporting   disease, were recorded. During the first 3 months of the study, pa-
of this study.                                                           tients who were due for their yearly laboratory evaluation had an
   Address reprint requests to Wayne R. Rackox MD, Section of            additional 0.5 to 1.0 mL of venous blood drawn for determination
Pediatric Hematolog}~Oncolog.v,     James Whitcomb Riley Hospital        of the oxygen dissociation curve and 2,3-disphosphoglycerate level.
fi,r Children, Indiana University Medical Center, 702 Barnhill Dr,       Patients without a history of hemoglobinopathy, anemia, or pulmo-
 Room 2720, Indianapolis, IN 46202-5225.                                 nary disease were recruited to serve as control subjects for these
   The publication costs of this article were defiayed in part by page   studies.
charge payment. This article must therefore be hereby marked                Patients were also enrolled in the emergency department at the
 “advertisement” in accordance with 18 U.S.C.section 1734 solely to      time of visits for acute illness. A medical history, including the
 indicate this fact.                                                     presence of respiratory signs and symptoms and pain, and labora-
   0 1993 by The American Society of Hemutology.                         tory data were recorded by the examining physician on a standard
   0006-4971/93/8212-0029$3.00/0                                         form. Oxygen dissociation curves were measured in a subset of Hb

3422                                                                                    Blood, Vol 81, No 12 (June 15), 1993:pp 3422-3427
PULSE OXIMETRY IN SICKLE CELL DISEASE                                                                                                  3423

SS patients. Arterial blood gases were measured at the discretion of        lower mean transcutaneous SaO, values (Table 1). These
the examining physician.                                                    associations were not seen in clinically well Hb SC patients
   Pulse oximetry. All patients were studied using one oftwo pulse          (Table I). In multivariate regression analysis, both a history
oximeters (Model N-200; Nellcor, Hayward, CA). The appropriate              of acute chest syndrome and older age were associated with
sensor was placed on the right index finger of older patients or the        lower transcutaneous SaO, in Hb SS patients ( P < .01 for
right big toe of infants. The transcutaneous SaO, was recorded
when a steady pulse and oxygen saturation read-out were obtained.
                                                                            both coefficients). The effect of a history of acute chest syn-
The pulse oximeters in the emergency department and clinic were             drome was significant despite long intervals since the last
compared using 26 normal adult volunteers; no pair of values was            episode (median, 10 months).
greater than 1 point different.                                                The effect of Hb F level was examined for 52 of the 86 Hb
   Oxygen dissociation curve, 2,3-diphosphoglycerate, and Hb                SS patients on whom data were obtained at study entry. As
F. Oxygen dissociation curves were measured at 37°C and pH                  expected, Hb F levels were significantly higher in those 5 5
7.40 by the continuous dual-spectrophotometric technique previ-             years old (mean, 18.1%k 12.7%; n = 24) than in patients
ously described by Asakura.' Specimens were preserved in EDTA,              older than 5 years (mean, 7.6% k 6.5%; n = 28; P < .OOl).
and kept on ice until they were tested; oxygen dissociation curve
                                                                            The Hb F levels of patients with a history of acute chest
measurements were made within 8 hours of specimen collection.
Quantitative 2,3-diphosphoglycerate levels were measured using              syndrome (mean, 9.9% f 8.4%; n = 30) were significantly
the method of Rose and Leibowitz." Hb F levels were determined              lower than those without a history of acute chest syndrome
by the alkali denaturation method.                                          (mean, 15.8%k 13.4%;n = 22; P = .008). The effects of age,
   Statistical analysis. Independent samples and paired t-tests             acute chest syndrome history, and Hb F level on transcuta-
were used to compare the means of continuous, normally distrib-             neous SaO, were examined in a multivariate regression anal-
uted variables. Hb F levels were not normally distributed. There-           ysis; a history of acute chest syndrome was associated with
fore, a normally distributed log transformation of these values was         lower transcutaneous SaO, (P = .007), lower Hb F levels
used in t-tests that compare mean Hb F levels. The Wilcoxon rank            were associated with lower transcutaneous SaO, ( P = .O 12),
sum test and the Kruskal-Wallis generalization of the Wilcoxon              and the effect of age on transcutaneous SaO, was not signifi-
rank sum test were used to compare the means of 2 2 groups when
                                                                            cant ( P = .459) when Hb F level was included in the model.
t-tests or analysis of variance (ANOVA)were inappropriate." The
Dunn procedure was used to compare pairs of groups under the                   Oxygen dissociation curves were measured in 32 of the 86
Kruskal-Wallis test." Univariate or multiple regression analysis            clinically well Hb SS patients, 12 of the 22 clinically well Hb
was used to estimate the effectsofindependent variables on continu-         SC patients, and 10 control subjects. As shown in Fig 1, the
ous dependent variables. All statistical tests were two-tailed. Means       curves for Hb SS patients were right-shifted when compared
are reported fI SD.                                                         with those of Hb SC patients and control subjects (com-
                                                                            pared at POzequal to 70,80, and 90 mm Hg; P < .OO I). As a
                              RESULTS                                       result of this shift, lower Hb oxygen saturation values repre-
   Pulse oximetry and oxygen dissociation curves in clini-                  sent higher PaO, values than would be predicted by a nor-
cally wellpatients. Resting transcutaneous SaO, was mea-                    mal oxygen dissociation curve. Although the curves of Hb
sured by pulse oximetry at routine clinic visits in 86 clini-               SC patients are right-shifted when compared with those of
cally well Hb SS patients, 22 clinically well Hb SC patients,               control subjects, the difference is not significant. This is de-
and 10 control subjects. Hb SS patients had a significantly                 spite the fact that the mean 2,3-diphosphoglycerate level for
lower mean resting transcutaneous SaO, than did patients                    Hb SC patients was significantly higher than that of control
with Hb SC or control subjects (Table 1). All Hb SC patients                subjects (5,634.2 5 844.0 nmol/mL red blood cells [RBC] v
had transcutaneous SaO, values that were in the normal                              *
                                                                            4,370 392.1 nmol/mL RBC; P I .05) and similar to Hb
range (96% to loo%), whereas 44.2% of Hb SS patients had                    SS patients (5,789.0 f 703.3 nmol/mL RBC).
transcutaneous SaO, values lower than 96%.                                     A lower Hb level is usually associated with a higher 2,3-
   In the Hb SS patients, a past history of acute chest syn-                diphosphoglycerate level and a more right-shifted oxygen
drome and age greater than 5 years were associated with                     dissociation curve. When the oxygen dissociation curve is

                                      Table 1. Transcutaneous SaOz Values in Clinically Well Patients

                                                                     ACS                                                    Age

 Group                      All                     No History                    History                          s 5 yr           z 5 yr
Hb SS                  95.6f 3.8*                  97.8? 2.3                   93.8f 3.9t                  97.2f 3.1              94.0k 3.9t
                          (86)                        (40)                        (46)                        (43)                   (43)
Hb SC                  99.1 fO.9                   99.1f 1.0                   99.1+- 0.7                  99.2k 1.0              99.0k 0.7
                          (22)                        (12)                        (10)                        (12)                   (10)
Control                99.0f 0.8                      -                           -                           -                      -
  Values are mean transcutaneous Sa02% ? 1 SD (n).
  Abbreviation: ACS, acute chest syndrome.
  * Kruskal-Wallis test P < ,001; Hb SS significantly different from Hb SC and control by Dunn procedure, cy   =   0.05
  t P < .001 for no history of ACS versus history of ACS and 15 years versus >5 years.
3424                                                                                                                  RACKOFF ET AL

                                                                        lated from patients’ oxygen dissociation curves and transcu-

   loo    I                                             Control
                                                        Hb SC
                                                                        taneous SaO, values is significantly lower for patients with a
                                                                        history of acute chest syndrome (76.6 -t 1 1.4 mm Hg) than
                                                                        for those with no history of acute chest syndrome (90.7
                                                                         12.9 mm Hg; P < .01).
                                                                           Pulse oximetry in acutely ill patients. Eight patients
                                                                        with Hb SC disease were studied in the emergency depart-
                                                                        ment at the time of visits for acute illness. One patient with
                                                                        acute chest syndrome presented with a transcutaneous SaO,
                                                                        of 88%. Hb SC patients seen for pain (n = 5) and fever (n =
                                                                        2) had transcutaneous SaO, values in the normal range
                                                                        (range, 96% to 100%;mean, 97.6% k 1.6%).
                                                                           Fifty-five patients with Hb SS disease were studied in the

     O 0 I

                        I             I             I             I
                                                                        emergency department at the time of visits for acute illness.
                                                                        Thirty-two ofthe 55 patients had pulse oximetry at both the
                                                                        time of acute illness and when clinically well. No patient
                                                                        whose transcutaneous SaO, was 296% or within 3 points of
         60           70            80            00            100     a measurement made when the patient was clinically well
                              PO2 (mm Hg)                               was diagnosed with acute chest syndrome, either in the
                                                                        emergency department or after admission to the hospital.
  Fig 1. Hb oxygen saturation at PO2 equal to 70,80, and 90 mm          Five of the 32 patients had transcutaneous SaO, values that
Hg for children with sickle cell disease and control subjects. Sym-     were less than 96% and more than 3 points lower than their
bols are mean Hb oxygen saturation (X)       and bars are 1 SD. Lines   transcutaneous SaO, when clinically well. Two of these pa-
are drawn to represent the shape of the oxygen dissociationcurve
constructed from mean Hb oxygen saturation values for each
                                                                        tients were diagnosed with acute chest syndrome in the
group. Hb SS patients are different from Hb SC and control sub-         emergency department, and a third patient had an emer-
jects at all three points (Kruskal-Wallis test, P < .001:Dunn proce-    gency department diagnosis of vaso-occlusive pain, but de-
dure,n = 0.05).                                                         veloped acute chest syndrome during the subsequent hospi-
                                                                        tal stay. A fourth patient, who had a history of asthma, was
                                                                        treated for bronchospasm and discharged. The fifth patient
right-shifted, the P,, is higher and the Hb oxygen saturation           was admitted with fever and acute abdominal pain asso-
at PO, equal to 70 mm Hg is lower. In Hb SC patients and in             ciated with a massive hair bezoar.
control subjects, lower Hb levels were associated with higher              Without a baseline transcutaneous SaO, value for com-
2,3-diphosphoglycerate levels ( P 5 .OO I), and higher 2,3-di-          parison, the evaluation of acutely ill Hb SS patients is diffi-
phosphoglycerate levels resulted in higher P,, measure-                 cult; the variability in oxygen dissociation curves means
ments ( P = .046) and lower Hb oxygen saturation at PO,                 that a wide range of transcutaneous SaO, values may repre-
equal to 70 mm Hg ( P = .043). In Hb SS patients, 2,3-di-               sent acceptable PaO, (Fig I). Therefore, we used data from
phosphoglycerate did not appear to mediate the effect of                oxygen dissociation curves to construct a nomogram that
anemia on the shape of the oxygen dissociation curve.                   relates Hb level when clinically well and transcutaneous
Lower Hb levels were associated with higher P,, measure-                Sa02when acutely ill to the chance that a patient has a PaO,
ments (P < .OOl) and lower Hb oxygen saturation at PO,                  greater than 70 mm Hg. Hb level when clinically well was
equal to 70 mm Hg ( P .001). However, there was not a                   used as a control variable because of the significant relation-
significant association between Hb level and 2,3-diphos-                ship between Hb level and Hb oxygen saturation at PO,
phoglycerate level ( P = .573) or between 2,3-diphosphoglyc-            equal to 70 mm Hg (see regression model below), and be-
erate level and P,, (P= .2 14) or the Hb oxygen saturation at           cause it is relatively stable and is usually available to the
PO, equal to 70 mm Hg ( P < ,931). Thus, the expected                   clinician in the emergency department. The threshold PaO,
relationship between Hb level, 2,3-diphosphoglycerate                   value of 70 mm Hg was chosen because exchange transfu-
level, and the shape of the Hb oxygen dissociation curve was            sion is advocated for patients with acute chest syndrome
seen in Hb SC patients and control subjects, but not in                 and PaO, less than 70 mm Hg while the patient is breathing
patients with Hb SS.                                                    supplemental oxygen.,
   For the 32 Hb SS patients who had an oxygen dissocia-                   The Hb oxygen saturation that corresponded to a PO, of
tion curve measured when clinically well, mean transcutane-             70 mm Hg was recorded from the oxygen dissociation
ous SaO, values were 92.4% ? 3.0% for those with a history              curves of 32 clinically well Hb SS patients in this study, I O
of acute chest syndrome (n = 13) and 97.3% k 4.7% for                   Hb SS patients seen in the emergency department during
those with no history of acute chest syndrome (n = 19). The             this study, and 33 clinically well Hb SS patients studied
lower transcutaneous SaO, values seen in Hb SS patients                 previously in the same laboratory. Mean Hb oxygen satura-
with a history of acute chest syndrome could represent nor-             tion values at PO, equal to 70 mm Hg were not significantly
mal PaO, values if these patients had more right-shifted                different among the three groups. Univariate regression
oxygen dissociation curves than patients without a history              analysis yielded the following results: (Hb oxygen saturation
of acute chest syndrome. However, the mean PaO, calcu-                  at PO, at 70 mm Hg) = 84.2 + ( 1.O X Hb level); r2 = .18 1 ;P
PULSE OXIMETRY IN SICKLE CELL DISEASE                                                                                          3425

< .001. The upper 95% confidence interval of the regression              Accuracy ofpulse oximetry. Nine arterial blood gas mea-
line was plotted as a threshold above which there is relative         surements were made in 7 acutely ill Hb SS patients. These
certainty that the measured Hb oxygen saturation repre-               patients also had oxygen dissociation curve measurements
sents a PaO, of greater than 70 mm Hg for a given Hb level            from simultaneously drawn specimens, and transcutaneous
(Fig 2).                                                              SaO, measured by pulse oximetry just before arterial punc-
   To gain insight into the clinical utility of the nomogram,         ture. For each patient, the Hb oxygen saturation was calcu-
we used it to classify the 55 Hb SS patients studied at the           lated using measured PaO, and the patient's oxygen dissocia-
time of visits to the emergency department for acute illness          tion curve. There was close agreement between the
into those likely to have PaO, greater than 70 mm Hg and              measured transcutaneous and calculated SaO, values (Y =
those in whom a lower PaO, was more likely. The occur-                .972; n = 9). In the one case when the measured PaO, was
rence of acute chest syndrome during that emergency de-               less than 50 mm Hg, the transcutaneous SaO, value (66%)
partment visit or the subsequent hospital admission was               was significantly lower than would be predicted from the
then examined. One of 40 patients whose transcutaneous                PaO, and oxygen dissociation curve (76%).
SaO, was above the line, in the area in which PaO, greater
than 70 mm Hg is likely, developed acute chest syndrome                                       DISCUSSION
after admission to the hospital. Fifteen of 5 5 patients in our          Pulse oximetry is well studied as an alternative to the
sample had transcutaneous SaO, values below the line. Of              invasive monitoring of arterial oxygen saturation,'-4 but
these 15,4 were diagnosed with acute chest syndrome in the            there are limited data on its use in patients with sickle cell
emergency department (transcutaneous SaO, range, 8 1% to              disease. Weston Smith et a18 showed the accuracy of pulse
88%),3 were admitted for fever or pain and developed acute            oximetry in three patients with acute chest syndrome by
chest syndrome while in the hospital, and 1 had a history of          using Hb oxygen saturation derived from the patient's oxy-
asthma and was treated for bronchospasm in the emergency              gen dissociation curve and measured PaO, to evaluate the
department. For our sample, having a transcutaneous SaO,              transcutaneous SaO, value.* Their report illustrated that
value above the nomogram line had a high negative predic-             pulse oximetry is accurate in patients with sickle cell disease
tive value when used as a test to rule out acute chest syn-           when differences in patients' oxygen dissociation curves are
drome; Hb SS patients with transcutaneous SaO, values in              taken into account. Our data agree with and extend these
the area above the line had a 98% probability of not having           findings. The arterial blood gas data, while limited, show
acute chest syndrome in the emergency department or devel-            that pulse oximetry is accurate in patients with Hb SS; there
oping it during a subsequent hospital admission. The posi-            was close agreement between measured transcutaneous
tive predictive value, the probability of having acute chest          SaO, and Hb oxygen saturation calculated from a patient's
syndrome with a transcutaneous SaO, value below the line,             oxygen dissociation curve and PaO,. In the 1 patient with
was 47%.                                                              severe hypoxemia, the agreement was not good. Increasing
                                                                      negative bias between transcutaneous SaO, and Hb oxygen
                                                                      saturation measured by blood oximetry at low saturation in
    97                                                                anemic patients has been shown by Severinghaus and
                                                                      Koh.I3 As the investigators point out, the error is protective,
    96                                                                in that the degree of desaturation is overestimated by pulse
                                                                         Vichinsky et a16 have questioned the accuracy of pulse
    95                                                                oximetry in patients with sickle cell disease. They reported
                                                                      wide variation between Hb oxygen saturation measured by
s   94                                                                pulse oximetry and blood oximetry in untransfused sickle
                                                                      cell patients. Increased levels of nonfunctional met-Hb and
;   93
                                                                      carboxy-Hb in untransfused patients with Hb SS may ex-
                                                                      plain these findings. Pulse oximeters measure oxy-Hb as a
                                                                      percentage of functional Hb (oxy-Hb plus deoxy-Hb).
    92                                                                Blood oximeters used in arterial blood gas laboratories mea-
                                                                      sure oxy-Hb as a percentage of total Hb (fractional Hb oxy-
                                                                      gen saturation), including nonfunctional met-Hb and car-
    91                                                                boxy-Hb. If a sickle cell patient has a low Hb and increased
                                                                      met-Hb and carboxy-Hb because of hemolysis, blood oxim-
                                                                      etry will result in a lower Hb oxygen saturation value than
         5       6         7        8        9        10        11    pulse oximetry. For example, one of the Hb SS patients in
                                                                      our study had a transcutaneous SaO, of 85% measured by
                               Hb (g/dl)                              pulse oximetry, and met-Hb and carboxy-Hb levels of 5.0%
                                                                      and 4.7%, respectively; the patient had a fractional Hb oxy-
   Fig 2. Nomogram for PaOz greater than 70 mm Hg in Hb SS
patients. Transcutaneous SaO, when acutely ill is plotted against
                                                                      gen saturation of 74% when measured in the blood gas labo-
Hb level when clinically well. PaO, greater than 70 mm Hg is likely   ratory. When the fractional Hb oxygen saturation value is
if the transcutaneous SaO, value is above the line.                   adjusted to reflect oxy-Hb as proportion of functional Hb,
3426                                                                                                                RACKOFF ET AL

the resultant value is 82%,which is close to the value mea-        ments less than 96% should be considered hypoxemic until
sured by pulse oximetry. The measured fractional Hb oxy-           proven otherwise, and that significant decreases from base-
gen saturation is a useful check on the accuracy of pulse          line transcutaneous SaO, are rarely associated with uncom-
oximetry, but must be adjusted to reflect only functional Hb       plicated vaso-occlusive pain or fever. Comparison with a
before a comparison is made. The comparison of measured            patient's transcutaneous SaO, when clinically well appears
transcutaneous SaO, and Hb oxygen saturation calculated            to be the best means of identifying whether hypoxemia is
from a patient's oxygen dissociation curve and PaO, is the         present, because it obviates the need to make assumptions
most appropriate check on the accuracy of pulse oximetry,          about the patient's oxygen dissociation curve. For Hb SS
because both methods are based on the measurement of               patients, the nomogram shown in Fig 2 may be an alterna-
oxy-Hb as a proportion of functional Hb.                           tive for predicting the hypoxemia associated with acute
   The striking difference between Hb SC and Hb SS pa-             chest syndrome when a baseline transcutaneous SaO, value
tients was an unexpected finding in this study. In contrast to     is not available. Additional prospective studies will be
Hb SS patients, all clinically well Hb SC patients had nor-        needed to validate our findings and define the best use of the
mal transcutaneous SaOz. Also, the oxygen dissociation             nomogram.
curves of Hb SC patients were significantly different from            We did not obtain serial measurements oftranscutaneous
those of Hb SS patients, despite similar mean 2,3-diphos-          SaO, on patients when they were clinically well. The fact
phoglycerate values for the two groups. In fact, the curves of     that patients with uncomplicated pain and fever had trans-
Hb SC patients, while somewhat right-shifted, were not sig-        cutaneous SaO, measurements that were similar to measure-
nificantly different from those of control subjects. The ex-       ments made when they were clinically well suggests that
pected relationship between Hb level, 2,3-diphosphoglycer-         there is little day to day variation in SaO, in the absence of
ate level, and the shape of the oxygen dissociation curve was      intervening acute chest syndrome or worsening chronic
seen in Hb SC patients and control subjects, but not in            lung disease. Our current practice is to include the measure-
patients with Hb SS disease. Hb S must have an effect on Hb        ment of transcutaneous SaO, as part of the routine evalua-
oxygen affinity that is different from the effect of 2,3-di-       tion of patients with sickle cell disease. This practice will
phosphoglycerate. In this respect, our data agree with the         provide data on the consistency of transcutaneous SaO,
findings of Seakins et       who showed that the oxygen af-        measurements in patients with sickle cell disease and allows
finity of Hb SS blood is associated with intracellular Hb S        for comparison between transcutaneous SaO, values ob-
concentration and not with 2,3-diphosphoglycerate con-             tained when the patient is clinically well and those mea-
tent.                                                              sured in the setting of acute illness.
   Despite the fact that children with Hb SC may suffer from          This study is the most extensive study to date on the use of
severe episodes of acute chest syndrome, and that the Hb SC        pulse oximetry to measure transcutaneous SaO, in children
                                                                   with sickle cell disease. Although only a small number of
patients in this study had a similar rate of past acute chest
                                                                   observations were made, the correlation between SaO, mea-
syndrome, they differed from children with Hb SS with re-
                                                                   sured by pulse oximetry and calculated values was excellent.
spect to the effect of a history of acute chest syndrome and
                                                                   The differences between Hb SS and Hb SC patients and the
age on transcutaneous SaO,. In clinically well patients with
                                                                   identification of factors associated with Hb oxygen desatura-
Hb SS, a history of acute chest syndrome and older age are
                                                                   tion in children with Hb SS raises questions about the natu-
associated with significant arterial Hb oxygen desaturation,
                                                                   ral history of pulmonary dysfunction in patients with sickle
whereas no effect is seen in patients with Hb SC. Multivari-       cell disease. Longitudinal studies will be needed to confirm
ate analysis suggests that older age represents decreasing Hb      our findings and answer these questions. We conclude that
F levels in Hb SS patients, because the effect of age on trans-    pulse oximetry is useful in the clinical care of patients with
cutaneous SaO, is not significant when controlling for Hb F        sickle cell disease. Its routine use in the clinic may help US to
level. Cross-sectional studies of pulmonary function in chil-      understand better the natural history of pulmonary dys-
dren with sickle cell disease have not identified older age, a     function in these patients; and, its appropriate use in the
 history of acute chest syndrome, or the SS phenotype as           emergency department can aid in the evaluation of patients
 factors associated with worse pulmonary function stud-            for hypoxemia associated with acute chest syndrome.
 ies.'5,'6 However, such studies were limited by the fact that
pulmonary function testing with spirometry is not usually                               ACKNOWLEDGMENT
 possible in children under 5 years of age, whereas the study        We thank the nurses and physicians of the Divisions of Hematol-
 of very young children is possible with pulse oximetry. Lon-      ogy and Emergency Medicine at The Children's Hospital of Phila-
gitudinal studies of patients from birth are needed to define      delphia, especially Wendy Bulgarelli, RN, Renee Cecil, RN, and
 further the factors associated with the progressive pulmo-        Jane Graves, LPN, for their help in patient recruitment and data
 nary dysfunction suggested by our findings, and to deter-         collection. Michael Reilly, PhD, and KO Uchida, MD, provided
 mine whether Hb oxygen desaturation in childhood is asso-         valuable assistance in performing oxygen dissociation curve and
                                                                   2,3-diphosphoglycerate measurements. Alan Cohen, MD, provided
 ciated with progressive pulmonary dysfunction later in life.      valuable critical comments on the manuscript. Nellcor, Inc, kindly
    For clinicians caring for children with sickle cell disease,   provided a pulse oximeter for use in this study.
 an important finding of this study is that pulse oximetry
 may be used to screen for hypoxemia in the acute setting if                                 REFERENCES
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PULSE OXIMETRY IN SICKLE CELL DISEASE                                                                                                    3427

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