Precise Quantification of Fever in Childhood Bacterial Meningitis *
Marja Anttila, M.D. Jaakko-Juhani Himberg, Ph.D., M.D.† *
Heikki Peltola, M.D.
Summary: Precise quantity of fever was determined in 191 cases of childhood bacterial meningitis by calculating the areas between the line indicating 37.8°C or 39.5°C temperature and the line connecting all individual temperature values. Temperature measurements were performed rectally one to four times a day throughout the hospitalization. The obtained areas under the curves (AUC), expressed as degree-hours, proved to be a sensitive index for delineating each individual fever pattern and reflected the magnitude of fever more precisely than the traditional fever curves. Children under five had significantly (p lJ)i illi 1 1. l #> I I§.,%].§]$#&diquo; atl§#x&dquoJ; x~[[[ig9’° §,j.[[ ) I §)# li§#j[, .[ )&dquo; ~ &°dq’uo§); #i , ]j .[&dq.[uo;..); %;j§·:.I ll:..:.. §#I [§ I,[11 li.:l’Ia §fl§i>.[[#[ f &d#quo; ,§. .’ioa, l’ii&diquoi;. * » ,#.§i Ii ’.i§ti.ni. lJj[%#$$m% ~ . 3 » ;.jg,jiii ~ . t i< §ffx ; §, ~ :? ,:. % o j h§)j§j §%§° #g #. =§ ’g&diquoz;%[_;’oI#[ ’I; ,§ #.[, : i#f ’ bflf %zY$k#~§§§#§ § § ’#_~l §I §_§iii% ~ §§ j yzjjjfig§g~@gjjij§jj ; ... ’@g)gjjjjj§ > ; .: :#. ’ , .. ~ ’~,# i’l ’§I;( ~# i;x: .§I# # £I. ~ § §# ) #&dquo; %&dquo; _ ~ , ,h ;£ , ; j§g w
;..
222
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Downloaded from cpj.sagepub.com at UNIV OF MICHIGAN on March 13, 2015
mea-
done six-hour inter-
which is used routinely in Finnish hospitals. The first afebrile day was defined as the first day with temperature below 37.8°C ( 100° F) for at least 24 hours. Secondaryfeverwas a temperature of38.0°C ( 101 °F) or higher occurring after at least one afebrile day and recorded on at
re-
° ~ &dquo;
comprised morning tempera-
a.m.
Temperature Measurement Rectal
on
ter one to
three antimicrobials were administered in four daily doses, ceftriaxone only once a day. All antimicrobials were given intravenously for seven days. Detailed analysis of aspects of this study other than fever have been published separately.6
Patients
During
regimens: 1)chloramphenicol
(KLO, 100 mg/kg/day); 2)ampicillin (AMP, 250 mg/kg/day, initiated with KLO); 3) cefotaxime (CTX, 150 mg/kg/day); and 4)ceftriaxone (CRO, 100 mg/kg/day). The first
,
,
= ... , ...... ..
,
.=
=
#
#§
a= ........ ~&dquo;‘:a : .,;.....=
:. ,..n..,
...,
.s,..
least two consecutive occasions. Two different limits for fever (37.8°C and 38.0°C) were chosen in order to compare our observations with the data published earlier.l,4-5 Persistent fever was defined as a temperature of 37.8°C or higher, lasting for five to nine days. If it persisted longer, it was called prolonged fever. The first hospital day was defined as the remaining hours before midnight after admission. Each patient’s fever was quantified at two levels. &dquo;Fever&dquo; was determined by calculating AUC beneath the line connecting daily temperature measurements and the line at 37.8°C. &dquo;High fever&dquo; was quantified by measuring only the area above the line at 39.5°C ( 103.1 °F) . The AUCs were calculated according to numeric estimation of area by the trapezoidal rule? and pro-
grammed on a Hewlett-Packard 85 desktop computer and expressed in degree-hours. The calculations were made separately for the first and the second week of hospitalization.
Recording of Complications Clinical checkups were done on discharge
and two
weeks, and
Table 2
fection was registered daily on a separate questionnaire. A skull transillumination was performed daily for patients whose skull thickness allowed reliable interpretation of the result; in practice, it was possible up to around two years of age. CT scan and other investigations were done if clinically relevant.
at
three, six, and 12 months thereaf-
Statistics
Complications were defined as neurological (impaired hearing, ataxia, hypotonia, hypertonia, cranial nerve palsy, hemiparesis, obstruction of cerebrospinal fluid flow, and subdural effusion), infective (pneumonia, otitis media, sinusitis, upper respiratory tract infection, gastroenteritis, herpes simplex virus infection, and varicella), or other complications (prolonged neck stiffness, skin necrosis, gastrointestinal bleeding, skin rash, reactive arthritis, suspected systemic lupus erythematosus, and ju-
Statistical analysis was performed using the standard chisquare test, with Yates’ correction for continuity and Fisher’s exact
ter.
venile rheumatoid arthritis). Potential occurrence of phlebitis, diarrhea, and superficial fungal in-
when
comparing frequencies, and one-way analysis of variance when comparing temtest
perature values. Because of
positive skewness of the distributions for the AUC values, statistical calculations for this parameter were made after logarithmic transformation using one-way analysis of variance; a probability value less than 0.05 was regarded as significant and less than 0.01 was regarded as
highly significant.
Results Patients A total of 200 evaluable cases were divided into 146 cases due to Haemophilus influenzae type B, 32 due to Neisseria meningitidis, 13 due to Streptococcus pneumoniae, and nine due to other bacteria (one group B streptococci, one E. coli) or to unknown causes. The age range was from three months to 15 years, with 87% of patients under five; 59% were boys and 41 % were
girls. Nine patients died. Fever of these children is not scrutinized here (because of multiplicity of special treatment maneuvers in these patients). The mean duration of hospital treatment was 13.7 days, with 76% of the patients being hospitalized from eight to 14 days and 24% longer than two weeks.
AUC The number of temperature varied slightly from
measurements
Downloaded from cpj.sagepub.com at UNIV OF MICHIGAN on March 13, 2015
223
1.
Figure areas
Geometric of the
chloramphenicol had greater (p
Marja Anttila, M.D. Jaakko-Juhani Himberg, Ph.D., M.D.† *
Heikki Peltola, M.D.
Summary: Precise quantity of fever was determined in 191 cases of childhood bacterial meningitis by calculating the areas between the line indicating 37.8°C or 39.5°C temperature and the line connecting all individual temperature values. Temperature measurements were performed rectally one to four times a day throughout the hospitalization. The obtained areas under the curves (AUC), expressed as degree-hours, proved to be a sensitive index for delineating each individual fever pattern and reflected the magnitude of fever more precisely than the traditional fever curves. Children under five had significantly (p lJ)i illi 1 1. l #> I I§.,%].§]$#&diquo; atl§#x&dquoJ; x~[[[ig9’° §,j.[[ ) I §)# li§#j[, .[ )&dquo; ~ &°dq’uo§); #i , ]j .[&dq.[uo;..); %;j§·:.I ll:..:.. §#I [§ I,[11 li.:l’Ia §fl§i>.[[#[ f &d#quo; ,§. .’ioa, l’ii&diquoi;. * » ,#.§i Ii ’.i§ti.ni. lJj[%#$$m% ~ . 3 » ;.jg,jiii ~ . t i< §ffx ; §, ~ :? ,:. % o j h§)j§j §%§° #g #. =§ ’g&diquoz;%[_;’oI#[ ’I; ,§ #.[, : i#f ’ bflf %zY$k#~§§§#§ § § ’#_~l §I §_§iii% ~ §§ j yzjjjfig§g~@gjjij§jj ; ... ’@g)gjjjjj§ > ; .: :#. ’ , .. ~ ’~,# i’l ’§I;( ~# i;x: .§I# # £I. ~ § §# ) #&dquo; %&dquo; _ ~ , ,h ;£ , ; j§g w
;..
222
.
*’
. . ’ § ’°
.. , i , &dquo;,,
*; a s,
&dquo; ’ &dquo;
6
_;
> °i, I’§ [. :, ,i
..
+
.a:
ii
i
§
..
~
‘:
&dquo;
t
§=,_;_,= §% ,. , ,_=. ~__~ , ~ ~..;, ; , l 1 :. ........t :i ::: . .......
~
...
&dquo;&dquo;...
:
n : yi! ± .1
,.,.~, :
#
_, ~
1
*
.. , .. .......... &dquo;.~,.a. := _
/
Downloaded from cpj.sagepub.com at UNIV OF MICHIGAN on March 13, 2015
mea-
done six-hour inter-
which is used routinely in Finnish hospitals. The first afebrile day was defined as the first day with temperature below 37.8°C ( 100° F) for at least 24 hours. Secondaryfeverwas a temperature of38.0°C ( 101 °F) or higher occurring after at least one afebrile day and recorded on at
re-
° ~ &dquo;
comprised morning tempera-
a.m.
Temperature Measurement Rectal
on
ter one to
three antimicrobials were administered in four daily doses, ceftriaxone only once a day. All antimicrobials were given intravenously for seven days. Detailed analysis of aspects of this study other than fever have been published separately.6
Patients
During
regimens: 1)chloramphenicol
(KLO, 100 mg/kg/day); 2)ampicillin (AMP, 250 mg/kg/day, initiated with KLO); 3) cefotaxime (CTX, 150 mg/kg/day); and 4)ceftriaxone (CRO, 100 mg/kg/day). The first
,
,
= ... , ...... ..
,
.=
=
#
#§
a= ........ ~&dquo;‘:a : .,;.....=
:. ,..n..,
...,
.s,..
least two consecutive occasions. Two different limits for fever (37.8°C and 38.0°C) were chosen in order to compare our observations with the data published earlier.l,4-5 Persistent fever was defined as a temperature of 37.8°C or higher, lasting for five to nine days. If it persisted longer, it was called prolonged fever. The first hospital day was defined as the remaining hours before midnight after admission. Each patient’s fever was quantified at two levels. &dquo;Fever&dquo; was determined by calculating AUC beneath the line connecting daily temperature measurements and the line at 37.8°C. &dquo;High fever&dquo; was quantified by measuring only the area above the line at 39.5°C ( 103.1 °F) . The AUCs were calculated according to numeric estimation of area by the trapezoidal rule? and pro-
grammed on a Hewlett-Packard 85 desktop computer and expressed in degree-hours. The calculations were made separately for the first and the second week of hospitalization.
Recording of Complications Clinical checkups were done on discharge
and two
weeks, and
Table 2
fection was registered daily on a separate questionnaire. A skull transillumination was performed daily for patients whose skull thickness allowed reliable interpretation of the result; in practice, it was possible up to around two years of age. CT scan and other investigations were done if clinically relevant.
at
three, six, and 12 months thereaf-
Statistics
Complications were defined as neurological (impaired hearing, ataxia, hypotonia, hypertonia, cranial nerve palsy, hemiparesis, obstruction of cerebrospinal fluid flow, and subdural effusion), infective (pneumonia, otitis media, sinusitis, upper respiratory tract infection, gastroenteritis, herpes simplex virus infection, and varicella), or other complications (prolonged neck stiffness, skin necrosis, gastrointestinal bleeding, skin rash, reactive arthritis, suspected systemic lupus erythematosus, and ju-
Statistical analysis was performed using the standard chisquare test, with Yates’ correction for continuity and Fisher’s exact
ter.
venile rheumatoid arthritis). Potential occurrence of phlebitis, diarrhea, and superficial fungal in-
when
comparing frequencies, and one-way analysis of variance when comparing temtest
perature values. Because of
positive skewness of the distributions for the AUC values, statistical calculations for this parameter were made after logarithmic transformation using one-way analysis of variance; a probability value less than 0.05 was regarded as significant and less than 0.01 was regarded as
highly significant.
Results Patients A total of 200 evaluable cases were divided into 146 cases due to Haemophilus influenzae type B, 32 due to Neisseria meningitidis, 13 due to Streptococcus pneumoniae, and nine due to other bacteria (one group B streptococci, one E. coli) or to unknown causes. The age range was from three months to 15 years, with 87% of patients under five; 59% were boys and 41 % were
girls. Nine patients died. Fever of these children is not scrutinized here (because of multiplicity of special treatment maneuvers in these patients). The mean duration of hospital treatment was 13.7 days, with 76% of the patients being hospitalized from eight to 14 days and 24% longer than two weeks.
AUC The number of temperature varied slightly from
measurements
Downloaded from cpj.sagepub.com at UNIV OF MICHIGAN on March 13, 2015
223
1.
Figure areas
Geometric of the
chloramphenicol had greater (p
