Acute severe hypertension associated with acute gastroenteritis in children

Abstract

Acute severe hypertension in otherwise healthy children with acute illness requiring hospitalization for BP management is uncommon and warrants immediate evaluation. We describe 10 cases of children presenting with acute gastroenteritis and found to have acute severe hypertension. They required admission to the hospital for antihypertensive treatment, including 2 to the intensive care unit, but all had normalization of BP and were able to stop treatment with resolution of the acute illness. All patients had thorough testing for secondary causes of hypertension and for signs of end‐target organ damage, which were unremarkable. To our knowledge, acute severe hypertension in the setting of acute gastroenteritis without underlying kidney pathology and with complete resolution after illness has not been previously described. The mechanism of this association is not clear, although activation of the sympathetic nervous system is suspected. These cases illustrate the importance of thoroughly assessing BP in the acute setting.

1. INTRODUCTION

Elevations in blood pressure (BP) among hospitalized patients are a common occurrence; however, they are usually attributed to the stress of the acute illness and environmental surroundings. Specific causes include pain in the setting of procedures, new medications such as corticosteroids or central nervous system stimulants, or to the stress of the hospitalization itself. ¹ In these situations, treatment is directed at the underlying cause, such as pain management, but antihypertensive treatment may not be necessary. Even if transient acute treatment is required, because there is a known source of the high BP, an extensive work‐up for cause of hypertension is not always required.

The 2017 American Academy of Pediatrics Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents discusses the diagnosis and evaluation of hypertension, focusing on the outpatient clinical setting. ² Specifically, the evaluation for secondary causes of hypertension is limited to those <6 years old or without strong suspicion for primary hypertension. In addition to a detail history and physical exam, the evaluation should include only limited laboratory and imaging testing based on the specific patient situation.

In contrast, in acute severe hypertension, the risks of organ damage and the likely necessity of treatment usually require broader initial testing of a potential cause of hypertension. ² , ³ Acute severe hypertension is an acute elevation in BP from baseline with potential for life‐threatening end organ damage. ¹ , ² , ⁴ There is not a clear consensus for cutoff BP values, but it is suggested that those with acute severe hypertension will have BP elevation well above the stage 2 hypertension threshold and that acute target organ effects are more likely when the BP is elevated to 30 mm Hg or more above the 95th percentile. ²

Acute elevations in BP are more often due to a secondary cause. ¹ , ² , ³ , ⁵ In patients with a secondary cause of hypertension, the most common etiology is dependent on patient age. Newborns are most likely to have congenital anatomic anomalies of the vascular or urogenital system while younger children are more likely to have renal parenchymal disease. ⁴ , ⁶ Other causes to consider include malignancy, endocrine or metabolic disorders, medication overdose, or illicit substance use. ⁴ , ⁶ In older children and adolescents, primary hypertension becomes much more common, including both new diagnoses as well as noncompliance with antihypertensive medication. ⁴ , ⁶ Overall, the most common causes of acute severe hypertension presenting to the emergency department are primary hypertension, renal parenchymal disease, and endocrine or metabolic disorders. ¹ , ⁵ , ⁷ , ⁸

To our knowledge, there are no published reports of acute severe hypertension being associated with acute gastroenteritis. In this case series, we present 10 cases of children who were diagnosed with presumed viral gastroenteritis and found to have acute severe hypertension, without any secondary cause of high BP and with complete resolution of the high BP after illness resolved. The mechanism of the association between acute gastroenteritis and elevations in BP is not clear, but these cases illustrate the importance of evaluating BP in the setting of acute illness.

2. CASE PRESENTATIONS

Herein, we report 10 cases of children who presented to a single tertiary center with presumed viral gastroenteritis and were found to have BP elevated to greater than the 99th percentile for age, sex, and height. The electronic health records of these patients were reviewed and the clinical presentation, diagnostic testing, treatment, and follow‐up after hospital discharge were collected and summarized. The study was approved by the Institutional Review Board of Northwell Health.

The children ranged in age from 3 to 10 years old (mean 7 ± 2 years), with 6 females and 4 males (Table 1). All had no previous medical history, specifically no underlying kidney disease or prior diagnosis of hypertension. Case 3 was born at 31‐week gestation but had no residual medical complications. The patients were given clinical diagnoses of presumed acute viral gastroenteritis based on their presenting signs and symptoms, which included vomiting, diarrhea, abdominal pain, and decreased oral intake. Three showed signs of mild dehydration based on physical examination findings. The presenting signs and symptoms of gastroenteritis were isolated episodes that resolved without specific intervention.

Table 1.

Patient cases demographics, diagnostic evaluation, and treatment

Case	Age (years)	Sex	Body mass index (kg/m2)	Max systolic BP (mm Hg)	Max diastolic BP (mm Hg)	Sodium, Serum (mmol/L)	Bicarbonate, Serum (mmol/L)	Hemoglobin, Serum (g/dL)	eGFR (mL/min/1.73 m2)	Medication dosage during admission	Length of admission (days)	Medication dosage on discharge	Length of treatment after discharge (weeks)
1	8	F	15.6	155	102	140	27	13.1	127	Amlodipine 0.1 mg/kg BID Enalapril 0.1 mg/kg BID Hydralazine 0.1 mg/kg Nifedipine ×2 0.1 mg/kg	4	Amlodipine 0.1 mg/kg BID Enalapril 0.1 mg/kg BID	24
2	10	M	23.9	180	124	135	22	12	94	Nicardipine 0.5 mcg/kg/min for 12 h Amlodipine 0.06 mg/kg BID Nifedipine 0.05 mg/kg Hydralazine 0.2 mg/kg	3	Amlodipine 0.06 mg/kg BID	8
3	5	F	12.5	140	100	139	18	14.9	150	Nicardipine 1 mcg/kg/min for 24 h Amlodipine 0.2 mg/kg BID	3	None	0
4	6	M	12.1	134	92	129	21	15.5	105	Amlodipine 0.03 mg/kg BID	2	None	0
5	9	F	20.3	152	123	137	26	15.3	100	Amlodipine 0.1 mg/kg BID Enalapril 0.1 mg/kg QD Nifedipine 0.1 mg/kg Hydralazine 0.1 mg/kg	5	Amlodipine 0.1 mg/kg BID Lisinopril 0.1 mg/kg QD	4
6	8	M	15.9	147	106	135	22	15.3	93	Amlodipine 0.1 mg/kg BID	3	Amlodipine 0.1 mg/kg BID	2
7	7	F	14.4	148	114	136	18	15.3	115	Amlodipine 0.125 mg/kg BID Enalapril 0.1 mg/kg QD Nifedipine 0.1‐0.2 mg/kg Hydralazine 0.1 mg/kg	3	Amlodipine 0.125 mg/kg BID Enalapril 0.1 mg/kg QD	5
8	3	F	13.9	165	98	138	22	12.5	144	Amlodipine 0.15 mg/kg BID Hydralazine 0.1‐0.15 mg/kg Nifedipine 0.1‐0.15 mg/kg	3	Amlodipine 0.15 mg/kg BID	2
9	8	F	15	136	96	139	18	13.4	106	Amlodipine 0.1 mg/kg BID Nifedipine 0.05 mg/kg	7	Amlodipine 0.1 mg/kg BID	2
10	6	M	19.8	149	96	136	20	13.4	180	Amlodipine 0.1 mg/kg BID Enalapril 0.1 mg/kg BID Hydralazine 0.1 mg/kg	4	Amlodipine 0.1 mg/kg BID Enalapril 0.1 mg/kg BID	1
Mean ± SD or N (%)	7 ± 2	4 M (40%)	16 ± 3.8	150 ± 14	105 ± 11	136 ± 3	21.4 ± 3.1	14 ± 1.3	121 ± 25		3.6 ± 1.3		4.8 ± 7

Abbreviations: BID,bis in die or twice per day; BP,blood pressure; eGFR,estimated glomerular filtration rate, calculated using the bedside Schwartz equation; F, female; M, male; QD, quaque die or once per day.

All patients presented with acute severe hypertension and thus received a comprehensive work‐up for secondary causes of high BP and for signs of target organ damage. All had serum complete blood count, metabolic panel, and renin and aldosterone level. Nine had urinalysis tested, 8 had thyroid function and metanephrines, and 4 had toxicology testing. Most had cardiac testing, specifically echocardiogram. Nine had renal ultrasound with Doppler, 4 had an MRI abdomen with renal angiography, and 7 had head imaging (CT or MRI). All testing was overall unremarkable (Table 1).

All 10 patients had persistently high BPs, even with appropriate pain, hydration, and symptom management and during sleep, and required hospital admission only for antihypertensive treatment (Table 1). Two required PICU admission for nicardipine infusion. All were started on amlodipine during admission, and 4 required a second standing agent. Six required hydralazine or nifedipine rescue medication to help control BP in addition to standing medication. The average length of admission was 3.6 ± 1.3 days (range 2 to 7 days).

Two had complete normalization of BP to <95th percentile during admission and were not discharged on any medication, including one that required nicardipine in the PICU. Eight were discharged on antihypertensive medication, 4 only on amlodipine, and 4 on amlodipine plus an angiotensin‐converting enzyme inhibitor. All did have complete resolution of high BPs and were able to discontinue medication on follow‐up in clinic (Table 1).

3. DISCUSSION

We present 10 cases of otherwise healthy children with presumed acute viral gastroenteritis found to have acute severe hypertension requiring antihypertensive treatment, without any secondary cause of hypertension and with complete normalization with resolution of the acute illness. To our knowledge, similar cases have not yet been reported in the literature.

Hypertension is known to be associated with bacterial diarrhea illness causing hemolytic uremic syndrome, resulting in kidney injury and possible chronic kidney disease. However, in a known outbreak of Escherichia coli O157:H7 gastroenteritis, children without hemolytic uremic syndrome did not have any increased risk of hypertension or reduced renal function years after their illness. ⁹ , ¹⁰ The cases presented here were presumed to have viral gastroenteritis based on signs and symptoms. There was no clinical indication to test stool samples for culture or polymerase chain reaction, given the mild nature of the gastroenteritis symptoms. All also had normal kidney function on laboratory testing and would not be expected to have any kidney injury causing high BP.

Acute severe hypertension in pediatrics is not common but is important to recognize in the acute care setting. Acute elevations in BP can cause target organ damage, most commonly retinopathy, encephalopathy, acute heart failure, and acute kidney injury. ⁵ , ¹¹ , ¹² These patients did not have evidence of target organ damage or malignant hypertension based on the unremarkable head and cardiac imaging as well as laboratory testing; however, they did not have fundoscopic examinations by an ophthalmologist, which are a potential limitation of the diagnosis of organ damage or malignant hypertension. Acute severe hypertension should be treated in order to prevent the potential for end organ damage. ⁵ , ¹¹ It is important to fully evaluate the potential underlying causes of acute severe hypertension in order to treat it effectively. It is unusual that these patient cases had no identifiable cause of their acute severe hypertension. Testing for secondary causes was negative, and the complete resolution of elevations in BPs indicates that there was not primary hypertension either. It is also uncertain why certain patients required continued antihypertensive treatment after discharge, as it did not seem to depend on patient characteristics or treatment required in the hospital, given that one patient who required nicardipine in the PICU was discharged on no medication.

The mechanism of acute severe hypertension in these patients is not clear. The etiology of acute severe hypertension is thought to be due to a combination of increased sympathetic activity, upregulation of the renin‐angiotensin‐aldosterone axis, and disruption of BP autoregulation. ¹ , ¹² , ¹³ The increase in sympathetic activity and in angiotensin causes vascular reactivity and vasoconstriction, as well as an inflammatory response. ¹ , ¹² , ¹³ The inflammation leads to more vasoconstriction and direct endothelial damage, as well as increased oxidative stress which causes additional vasoconstriction and endothelial dysfunction. ¹² , ¹³ In addition, there is a disruption in the normal BP autoregulatory system, which results in mechanical stress and endothelial damage, and finally tissue ischemia, leading to the end organ damage possible in acute severe hypertension. ¹² , ¹³ The initial upregulation of the sympathetic nervous system induces a cycle of vasoconstriction, inflammation, vascular damage, and ischemia. ¹² It could be hypothesized that in the setting of an acute illness, such as viral gastroenteritis, activation of the sympathetic nervous system initiates a cascade leading to acute severe hypertension.

It could be considered that dehydration due to gastroenteritis upregulated the sympathetic nervous system, but the vomiting and diarrhea in these patients were mild and only three showed any dehydration. Moreover, the elevations in BP persisted after rehydration; thus, it is unlikely that dehydration only is responsible for the extent of hypertension. Another possibility is a hypertensive pseudocrisis, in which patients who may have prior history of primary hypertension have elevated BP with symptoms such as headache, atypical chest or abdominal pain, and dysphagia in the setting of an acute event such as psychological stress, panic disorder, migraine, vertigo, or severe pain. ¹⁴ , ¹⁵ Similarly, there is no true target organ damage and resolution of the hypertension after the episode. ¹⁴ , ¹⁵ This diagnosis is less likely because the hypertension persisted even with pain and symptom management and during sleep, and did not recur.

In patients with cyclic vomiting syndrome (CVS) associated with hypertension, it is thought that the elevation in BP is due to hyperreactivity of the hypothalamic‐pituitary‐adrenal axis and increase in corticotropin‐releasing factor. ¹⁶ However, in CVS the episodes are recurrent and in the presented patients the episodes were isolated. The role of activation of the neuroendocrine system is supported by the complete normalization of the high BPs with resolution of the acute illness.

4. CONCLUSIONS

In this case series, we present 10 patients who were diagnosed with acute viral gastroenteritis and were found to have acute severe hypertension requiring hospitalization for antihypertensive treatment. All cases had completely negative testing for underlying cause of hypertension and had complete normalization of BP with resolution of the acute illness. These cases highlight the importance of evaluating for and investigating high BP in the setting of acute illness, both in hospitalized patients and in the outpatient setting. Future studies could help to elucidate the mechanism for this relationship.

CONFLICT OF INTEREST

None.

AUTHOR CONTRIBUTIONS

Jennifer Fishbein and Laura Castellanos‐Reyes contributed to study design, data collection, and writing of the manuscript. Christine Sethna and Pamela Singer contributed to study design and editing of the manuscript.

Fishbein JE, Sethna CB, Singer P, Castellanos L. Acute severe hypertension associated with acute gastroenteritis in children. J Clin Hypertens. 2020;22:2141–2145. 10.1111/jch.14029