Orthostatic Hypotension in Children with Acute Febrile Illness

Orthostatic Hypotension in Children with Acute Febrile Illness

The Journal of Emergency Medicine, Vol. 44, No. 1, pp. 23–27, 2013 Copyright Ó 2013 Elsevier Inc. Printed in the USA. All rights reserved 0736-4679/$ ...

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The Journal of Emergency Medicine, Vol. 44, No. 1, pp. 23–27, 2013 Copyright Ó 2013 Elsevier Inc. Printed in the USA. All rights reserved 0736-4679/$ - see front matter

doi:10.1016/j.jemermed.2012.02.045

Original Contributions

ORTHOSTATIC HYPOTENSION IN CHILDREN WITH ACUTE FEBRILE ILLNESS Tzippora Shalem, MD,*1 Michael Goldman, MD,*†1 Rachel Breitbart, MD,‡ Wendy Baram, RN,‡ and Eran Kozer, MD†‡ *Department of Pediatrics, Assaf Harofeh Medical Center, Zerifin, Israel, †Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, and ‡Pediatric Emergency Unit, Assaf Harofeh Medical Center, Zerifin, Israel Reprint Address: Eran Kozer, MD, Pediatric Emergency, Assaf Harofeh Medical Center, Zerifin 70300, Israel

, Abstract—Background: Children presenting to the Pediatric Emergency Department (PED) with fever often describe symptoms such as lightheadedness, dizziness, fatigue, and weakness, and may appear pale. They may also present with a chief complaint of syncope. Such symptoms may result from orthostatic hypotension. Objective: To determine whether children with an acute febrile illness have a higher incidence of orthostatic hypotension compared to afebrile children. Methods: A prospective cohort study was conducted at the PED at Assaf Harofeh Medical Center, a universityaffiliated hospital in Israel. Eighty children aged 4–18 years were recruited. Thirty-nine had fever (>38  C for 6–48 h) and 41 were afebrile. All subjects had their blood pressure measured in the supine position (after 5 min of rest) and again after standing for 3 min. The main outcome measure was orthostatic hypotension, that is, a reduction of systolic blood pressure of at least 20 mm Hg, or a fall in diastolic blood pressure of at least 10 mm Hg within 3 min of standing. Results: There were no differences between the groups in gender, age, height, or weight. Orthostatic hypotension was found in 10/39 (25.6%) of febrile children and in 2/41 (5%) of afebrile children (p = 0.012). Conclusions: The incidence of orthostatic hypotension among febrile children in the PED is high, and may explain common symptoms such as dizziness or syncope. Such patients should be instructed to drink properly and to avoid rapid changes in body posture. Ó 2013 Elsevier Inc.

INTRODUCTION Orthostatic hypotension occurs when the autonomic nervous system fails to maintain a stable blood pressure in the face of postural change (1,2). It is defined as a reduction of systolic blood pressure of at least 20 mm Hg, or diastolic blood pressure of at least 10 mm Hg within 3 min of standing (1,3,4). In human beings, upright posture is a fundamental stressor requiring an adequate blood volume, and rapid and effective circulatory and neurologic compensation to maintain blood pressure and consciousness (5). Orthostatic intolerance can result from volume depletion when the defense mechanism fails to maintain adequate venous return to the heart. It can also be caused by autonomic failure when the defense mechanism fails to respond adequately to postural change. A variety of conditions can cause orthostatic hypotension: alcohol and drugs (e.g., alpha- and beta-blockers, calcium channel blockers, tricyclic antidepressants, and opiates), volume depletion, and autonomic failure (5–8). Children presenting to the Pediatric Emergency Department (PED) with fever often describe symptoms such as lightheadedness, dizziness, fatigue, and weakness, and may appear pale. They may also present with a chief complaint of syncope. Such symptoms may result from orthostatic hypotension (9). We hypothesized that fever may be associated with autonomic changes (e.g., vasodilatation) that may lead to orthostatic hypotension.

, Keywords—blood pressure; fever; orthostatic hypotension; syncope 1

These authors contributed equally to the study.

RECEIVED: 18 August 2011; FINAL SUBMISSION RECEIVED: 11 November 2011; ACCEPTED: 22 February 2012 23

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The objective of the present study was to determine if children with an acute febrile illness have high incidence of orthostatic hypotension. PATIENTS AND METHODS A prospective cohort study was conducted at the ED of Assaf Harofeh Medical Center, a university affiliated hospital in Israel. Children aged 4–18 years referred to the PED due to fever (temperature > 38  C) lasting < 48 h and who had temperature of 38  C or higher in the PED, were compared to children of the same age presenting to the PED without a history of fever and who did not have fever in the PED. Patients were excluded if they presented with a chief complaint of syncope or near syncope, suffered from vomiting or diarrhea, showed signs of dehydration, or were suspected of having central nervous system infection. Patients were also excluded if they were being treated with medications that may alter blood pressure, or had a known chronic disease or a history of recurrent syncope. After obtaining informed consent, caregivers of eligible patients were asked to fill out a questionnaire that included questions on demographic data (age, sex), duration of fever, other symptoms, chronic illness, and medications. Based on the child age and level of cooperation, temperature was measured orally or rectally. Blood pressure was measured with an automated sphygmomanometer (Spot Vital Signs 420, Welch Allyn, Beaverton, OR) using a cuff covering 2/3 of the child’s upper arm. Blood pressure was first measured in the supine position after 5 min of bed rest. The patient was then asked to stand, and a second blood pressure measurement was carried out after 3 min of standing. A urine sample was collected for specific gravity. Orthostatic hypotension was defined as a reduction of systolic blood pressure of at least 20 mm Hg, or a fall in diastolic blood pressure of at least 10 mm Hg within 3 min of standing (1,3,4). Because we could not find data on the frequency of orthostatic hypotension among patients in the pediatric PED, we were unable to perform formal power calculations. We aimed for a convenience sample of 40 patients in each group. The study protocol was approved by the hospital ethics board and was registered with clinicaltrials.gov as NCT00452712. Data Analysis Statistical analysis was conducted using PASW Statistics 17 (SPSS, Inc., 2009, Chicago, IL). Descriptive statistics were used to describe the study population. Children with

Table 1. Characteristics of the Study Patients Variable (Mean 6 SD)

Fever

No Fever

Age 10.1 6 3.8 10.9 6 3.9 (years) 6 SD Gender 18 21 (male) Height 139.13 6 25.3 140.50 6 18.8 (cm) 6 SD Weight 35.1 6 14.9 39.48 6 17.3 (kg) 6 SD

p-Value Test Used 0.355

t-test

0.5 0.852

Chisquared t-test

0.275

t-test

febrile disease were compared with children without fever using the Fisher’s exact test for categorical variables and the Student’s t-test for continuous variables. The level of significance for all variables was 0.05. RESULTS Ninety-seven children were evaluated for the study: 53 without fever – of whom eight refused to provide informed consent, and four failed to meet the study criteria (three with previous episodes of syncope and one patient with asthma). Of 44 children with fever, an informed consent could not be obtained in five. Hence, 80 children were included in the analysis – 39 with fever and 41 without fever. The characteristics of the study population are presented in Table 1. There were no differences in age, weight, height, or gender distribution between the two groups. Table 2 presents the final diagnoses of the patients. The vital sign measurements are presented in Table 3. Febrile children had a higher pulse rate in both the supine and erect positions. There were no differences in initial systolic or diastolic blood pressures between the groups. Orthostatic hypotension was found in 10 (25.6%) children who had fever and in two (4.9%) children without fever (p = 0.012). The mean urine-specific gravity was 1.0147 6 0.006 in febrile children and 1.015 + 0.006 in afebrile children (p = 0.9). Table 2. Final Diagnoses of Study Patients Diagnosis

Fever

No Fever

Abdominal pain Headache Laceration Fever with no focus Smoke inhalation Pneumonia Tonsillitis Cellulitis Urinary tract infection Urticaria Other Total

3 12 4 8 3 3 1 5 39

15 2 11 1 12 41

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Table 3. Blood Pressure, Pulse, Urine-specific Gravity and Orthostatic Hypotension in Children With and Without Fever Variable (Mean 6 SD)

Fever

No Fever

p-Value

Test Used

Temperature in ED ( C) Systolic blood pressure (supine) Diastolic blood pressure (supine) Pulse (supine) Systolic blood pressure (erect) Diastolic blood pressure (erect) Pulse (erect) Urine-specific gravity Orthostatic hypotension/Total

38.5 6 0.8 109.23 6 11.3 60.49 6 8.9 108.26 6 20.26 106.18 6 12.4 58.95 6 12.961 119.41 6 27.299 1.014 6 .0062 10/39

36.7 6 0.3 106.76 6 10.1 58.66 6 9.4 83.49 6 16.8 107.78 6 11.1 62.20 6 9.735 91.88 6 16.894 1.015 6 .0061 2/41

<0.0001 0.306 0.376 <0.0001 0.545 0.208 <0.0001 0.9 0.012

t-test t-test t-test t-test t-test t-test t-test t-test Fisher’s exact test

ED = Emergency Department.

DISCUSSION In a prospective study of children presenting to the PED, 25% of the children who had fever also had orthostatic hypotension. The incidence of orthostatic hypotension was much lower among non-febrile children. One possible explanation for the high incidence of orthostatic hypotension in febrile children is dehydration. Children with fever may have reduced appetite and may drink less than usual. We excluded patients with symptoms such as vomiting and diarrhea, which may lead to dehydration. Moreover, none of the children presented with clinical signs of significant dehydration (such as dry mucus membranes, delayed capillary refill, slow skin turgor, or weak peripheral pulses), and the urine-specific gravity and the reported interval from last meal was similar in both groups. It is also important to point out that none of the febrile children suffered from sepsis. We believe other mechanisms contributed to the observed high incidence of orthostatic changes in febrile children. Febrile children had higher pulse rates than did the afebrile children. As shown in the past, body temperature is an independent determinant of heart rate, causing an increase of approximately 10 beats/min per degree centigrade (10). The main mechanism for increasing cardiac output in children is increasing heart rate. One may assume that febrile children with a higher baseline heart rate may not be able to increase their heart rate and cardiac output appropriately. The finding of the current study may have practical implications. Based on these findings, it will be reasonable to advise febrile children to increase their fluid intake and to avoid rapid changes in body posture. Children who experienced syncope or near syncope during febrile illness may seek medical advice. Physicians should be aware that the syncope may result from orthostatic hypotension. If the child looks otherwise well, one may not need to proceed to further work-up. All the patients in the study had been febrile for < 48 h. The incidence of orthostatic hypotension may be higher with longer duration of fever, although this hypothesis should be tested in future studies.

A previous study in adults found a higher risk for fall accidents in elderly patients who had febrile disease (11). In that study, the patients were not examined for orthostatic changes. However, the results of our study, if repeated in adults, may partly explain that observation. Limitations The current study has several limitations. The sample was relatively small. The children were recruited by physicians aware of the research hypothesis. We did not use a case control approach because the strict exclusion criteria made it difficult to recruit patients, and we had to screen large numbers of patients to recruit each patient. Because the screening process was not properly documented, the possibility of selection bias cannot be ruled out. To reduce the possibility of selection bias, children presenting with syncope were excluded. Due to technical problems, we could not perform a follow-up blood pressure measurement (supine and after 3 min of standing) in the children with orthostatic hypotension when they were healthy and afebrile. CONCLUSION We found a high incidence of orthostatic hypotension in febrile children. In febrile children we therefore recommend avoiding rising quickly from the supine position. When taking care of an ill child, caregivers should encourage a high fluid intake. Physicians should consider whether there is a need for extensive work-up of a child who presents to the PED with syncope during a febrile illness. In a child who proves to be orthostatic, a big secondary work-up in addition to looking for the source of the fever is not necessary. REFERENCES 1. Goldschlager N, Epstein AE, Grubb BP, et al. for the practice guidelines subcommittee, North American Society of Pacing and electrophysiology: etiologic considerations in the patient with syncope and an apparently normal heart. Arch Intern Med 2003;163:151–62. 2. Stewart MJ. Autonomic nervous system dysfunction in adolescents with postural orthostatic tachycardia syndrome and chronic

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T. Shalem et al. fatigue syndrome is characterized by attenuated vagal baroreflex and potentiated sympathetic vasomotion. Pediatr Res 2000;48: 218–26. The Consensus Committee of the American Autonomic Society and the American Academy of Neurology. Consensus statement on the definition of orthostatic hypotension, pure autonomic failure, and multiple system atrophy. Neurology 1996;46:1470. Richard FL, Donald DB, Richard LD. Degowin’s diagnostic examination, 8th edn. Iowa City, IA: 2004. Stewart MJ. Orthostatic intolerance in pediatrics. J Pediatr 2002; 140:404–11. Rudolph CD, Rudolph AM, Hostetter MK, Lister G, Siegel NJ. Rudolph’s pediatrics. 21st edn. New York: McGraw-Hill; 2003.

7. Lewin MAG. Syncope (NMS) in adolescents. Paediatr Croat 2003; 47:61–3. 8. Narkiewicz K, Cooley RL, Somers VK. Alcohol potentiates orthostatic hypotension: implications for alcohol-related syncope. Circulation 2000;101:398–402. 9. Stewart MJ. Transient orthostatic hypotension is common in adolescents. J Pediatr 2002;140:418–23. 10. Davies P, Maconochie I. The relationship between body temperature, heart rate and respiratory rate in children. Emerg Med J 2009;26:641–3. 11. Shalameh F, Cassuto N, Oliven A. A simplified fall-risk assessment tool for patients hospitalized in medical wards. Isr Med Assoc J 2008;10:125–9.

Orthostatic Hypotension during Fever

ARTICLE SUMMARY 1. Why is this topic important? Children presenting to the Pediatric Emergency Department (PED) with fever often describe symptoms such as lightheadedness, dizziness, fatigue, and weakness, and may appear pale. These symptoms may result from orthostatic hypotension. 2. What does this study attempt to show? The objective of the present study was to determine if children with an acute febrile illness have high incidence of orthostatic hypotension. 3. What are the key findings? Twenty five percent of the children who had fever also had orthostatic hypotension. The incidence of orthostatic hypotension was much lower among non-febrile children. 4. How is patient care impacted? Based on these findings, it will be reasonable to advise febrile children to increase their fluid intake and to avoid rapid changes in body posture. Physicians should consider whether there is a need for extensive work-up of a child who presents to the PED with syncope during a febrile illness.

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