Hypertension acquired in paediatric critical patients is a recognised challenge, with variable reported frequency. Pain, agitation, and/or medications such as beta stimulants and corticosteroids are risk factors. Moreover, using sympathomimetics in shocked patients can cause acquired high blood pressure. Reference Olgun and John1 Cardiac output and systemic vascular resistance are multiplied together to determine blood pressure. The development of hypertension may, in theory, be caused by increased myocardial contractility and excessive adrenergic stimulation, which is the most likely aetiology. Reference Salgado, Silva and Vincent2 Treatment options are influenced by the pathophysiology of hypertension and whether systemic vascular resistance or cardiac output is the primary mechanism. Beta-blockers and calcium channel blockers, for example, have different mechanisms of action that can be useful or inappropriate depending on the unique pathophysiology of each patient.
Theoretically, an adaptation mechanism for elevated afterload is growth in left ventricular wall mass and thickness. Adult studies have revealed a poor or non-existent relationship between blood pressure and left ventricular wall mass. Reference de la Sierra, Coca, Pare, Sanchez, Valls and Urbano-Marquez4-Reference Palatini, Majahalme and Amerena6 This strengthens the impact of non-haemodynamic elements on left ventricular wall mass development. These include insulin, the renin-angiotensin-aldosterone system, sodium consumption, and growth factors such as catecholamines. Reference Yamori, Mori and Nishio7 It is well known that sympathetic tone has a trophic effect on the heart muscle. Reference Simpson8-Reference Kaypakli, Gür and Gözükara10 According to multicentre research, in children with newly diagnosed hypertension, abnormal left ventricular mass index occurs often, and neither the severity of hypertension nor the abnormal findings are associated with the development of left ventricular hypertrophy. Reference Liu, Hou and Hou11 Ventricular wall stress occurs in hypertensive children and eventually results in left ventricular hypertrophy or remodelling. Reference Mclntosh, Tong, Deakyne, Davidson and Scott12 The objective of this study was to evaluate the pathophysiology of acquired hypertension among paediatric critical patients in terms of cardiac index and systemic vascular resistance, as well as its influence on myocardial performance and left ventricular mass index, with the aim of guiding the choice of antihypertensive drugs. The secondary objective was to investigate whether paediatric intensive care unit-acquired hypertension was related to mortality or long hospital stay.
Method
We conducted a prospective observational cohort study on 121 critically ill infants and children aged from 1 month to 13 years who were admitted to the paediatric intensive care unit of Cairo University Children’s Hospital in 2021. The study received ethical committee approval and an Institutional Review Board number.
The children were divided into two groups: those critically ill with paediatric intensive care unit-acquired hypertension (n = 59) and those without paediatric intensive care unit-acquired hypertension (n = 62). We excluded patients known to have systemic hypertension, chronic kidney disease, aortic coarctation, or steroid therapy before admission, as well as patients who received systemic steroids during their paediatric intensive care unit stay. The following data were recorded on admission to the paediatric intensive care unit: age, sex, weight, and main system failure at admission. Vital signs including heart rate, respiratory rate, temperature, and blood pressure were taken for patients on inotropic support, and a vasoactive inotropic score was calculated, Reference Suprawoto, Nurhaeni and Waluyanti13 as was patients’ cumulative fluid balance (positive balance ≥10% of body weight).
Haemodynamic parameters, including cardiac index and systemic vascular resistance index, were recorded at the time of hypertension diagnosis using electrical cardiometry. The myocardial performance index of the left ventricle and left ventricular mass index were measured using transthoracic echocardiography. Urine output and serum creatinine were measured to estimate the burden of acute kidney injury. Days of mechanical ventilation (for ventilated patients) and paediatric sedation state scale were also recorded. Length of hospital stay and mortality risk were measured using the paediatric sequential organ failure assessment score. The adequacy of sedation among ventilated children was assessed using the COMFORT scale. Reference Araujo-Moura, Souza and Mello14 Cardiometry and echocardiography data collection was performed after the withdrawal of all inotropes and vasopressors to avoid effects on systemic vascular resistance index and cardiac output.
Blood pressure was measured non-invasively using automated oscillometric cuff readings from bedside paediatric intensive care unit monitors (Vismo Nihon Kohden). When hypertension was diagnosed, a verification measurement was conducted using a portable mercury device. According to one meta-analysis, automatic blood pressure monitors have strong measurement validity when compared with the mercury column. Reference Nagueh, Smiseth and Appleton15 Thus, these can be safely used in blood pressure measurements of children and adolescents in clinical and epidemiological studies.
Appropriate cuff size was used to avoid under- or over-estimation of readings, ensuring bladder length of 80–100% of arm circumference and bladder width of at least 40%. Measurements were taken using the right arm, which is the standard site of measurement. We used the new definition of hypertension adapted in 2017 by the American Academy of Pediatrics. For diagnosis of hypertension for patients aged under 13 years, we used a cut-off of blood pressure levels ≥95th percentile for age, sex, and height; for patients 13 and older, we used a fixed cut-off of ≥130/80 mmHg independent of age, sex, and height.
In the paediatric intensive care unit, three new systolic and/or diastolic readings events above 95th percentiles over 24 hours were required to diagnose acquired hypertension. The blood pressure levels were interpreted based on gender, age, and height and according to the American Academy of Pediatrics’ 2017 definition.
Electrical cardiometry (Aesculon; Osypka Medical, Berlin, Germany) was applied to ascertain the haemodynamic parameters of cardiac output, cardiac index, heart rate, and systemic vascular resistance index. Electrical cardiometry was set to record measurements at 1-minute intervals and to define five continuous and qualified signals (i.e., signal quality index, provided by Aesculon, ≥70%) over the duration of 5 minutes.
In terms of echocardiography parameters, the myocardial performance index of the left ventricle was measured and analysed by a paediatric cardiologist. Studies were done for cases of a supine or left lateral position using a Vivid S 5 series system with a probe of 3 or 6 MHz, depending on the patient’s age. The myocardial performance index of the left ventricle was measured by applying a tissue Doppler to the lateral mitral annulus. A pulsed Doppler sample volume was placed at the tips of the mitral leaflets, and the recorded transmitral velocity pattern was composed of two principal deflections used to measure ventricular relaxation: the E wave, occurring during the rapid filling phase, and the lower A wave, arising from atrial contraction. Diastolic dysfunction measured by the E/A wave ratio according to Reference Mizukoshi, Takeuchi, Nagata, Addetia, Lang, Akashi and Otsuji16 left ventricular diastolic dysfunction was present if: E/A ratio <1, The isovolumic relaxation time left ventricular mass index >100 m/s, and diastolic time >220 m/s (impaired relaxation pattern); pseudo-normalization resembling the normal configuration with respect to the mitral inflow but with low diastolic time and the restrictive pattern is present when E/A ratio >2, The isovolumic relaxation time <70 m/s, and diastolic time <150 m/s.
The following calculations were used to measure myocardial performance index of the left ventricle, left ventricular wall mass, and left ventricular mass index:
LVEDD = left ventricle end-diastolic dimension (mm), IVSd = septal thickness at end-diastole (mm), and PWD = posterior wall thickness at end-diastole (mm).
For each patient, the mean myocardial performance index value was calculated by dividing the sum of the two values (septum and lateral) by two. Left ventricular mass index was calculated by two-dimensional transthoracic echocardiography-guided M-mode measurements using the following equations: where LVEDD = left ventricle end-diastolic dimension (mm), IVSd = septal thickness at end-diastole (mm), and PWD = posterior wall thickness at end-diastole (mm). Reference Ehrmann, Selewski, Troost, Hieber and Gipson17
Studies were performed on 10 healthy children before the start of the present study to evaluate inter-observer and intra-observer reproducibility. The paediatric cardiologist and the intensivist were blinded to each other’s results and alternately performed two measurements on each patient. Intra-observer reproducibility was assessed between the observations by the same observer. The intensivist performed the echocardiography, and all the stored images were reviewed by the expert paediatric cardiologist.
Statistical methods
Statistics were used to describe patient data when appropriate, including the range, mean, standard deviation, median, frequencies (number of instances), and relative frequencies (percentages). When employing independent samples with data that were not normally distributed, the Mann–Whitney U test was used to compare quantitative variables between the research groups. The statistical significance of the difference between the two population means was evaluated using the Student’s t-test. Comparing categorical data requires a Chi-square test. When the anticipated frequency was less than 5, an exact test was utilised in its place. Statistical significance was defined as a probability value (p) of less than 0.05. All statistical calculations were performed using Microsoft Excel 2016 (Microsoft Corporation, NY, USA) and SPSS (Statistical Package for the Social Science; SPSS Inc., Chicago, IL, USA) version 15 for Microsoft Windows.
Results
Two groups of critically ill children admitted in 2021 were enrolled in the study: one group included those with paediatric intensive care unit-acquired hypertension (n = 59) while the other group did not have hypertension (n = 63). Both groups’ clinical and laboratory characteristics are shown in Table 1. These patients represent 14% of total admissions in 2021.
Table 1. Demographic and clinical variables between PICU-acquired hypertension and no hypertension group.
pSOFA=paediatric sequential organ failure assessment; VIS=vasoactive inotropic score; BMI=body mass index; CVP=central venous pressure; AKI=acute kidney injury; KDIGO=kidney disease improving global outcome.
There was no distinction between the two groups regarding age, gender, diagnosis, vasoactive inotropic score, paediatric sequential organ failure assessment score, pain score, fluid balance, or acute kidney injury. As shown in Table 1, the hypertension group had a longer duration of stay than the group with no blood pressure elevation (<0.0001), but there was no difference in mortality.
Haemodynamic parameters and echocardiography of the study group
Critically ill children with paediatric intensive care unit-acquired hypertension had a higher cardiac index (p = 0.0001), systemic vascular resistance index (<0.0001), left ventricular performance (0.037), and left ventricular mass index (0.009) compared to critical children without paediatric intensive care unit-acquired hypertension. Grade 1 diastolic dysfunction was observed more in patients with acquired blood pressure elevation, but with no statistical significance (Table 2).
Table 2. Difference in haemodynamic parameters between patients with ICU-acquired hypertension and no PICU-acquired hypertension.
CI=cardiac index; SVRI=systemic vascular resistance index; LVMPI=left ventricular myocardial performance index; LVMI=left ventricular mass index.
The multivariate logistic regression analysis showed that the paediatric sequential organ failure assessment score was the only predictor for the development of acquired hypertension (Table 3).
Table 3. Results of multivariable binary logistic regression analysis for predictors of hypertension.
Discussion
The results of our study showed an incidence of paediatric intensive care unit-acquired elevated blood pressure of 14% over a 1-year study period. Data about the prevalence of hypertension in paediatric intensive care units are scant. A prevalence of 25% was reported by Ehrmann et al., Reference Balestracci, Capone, Toledo and Sticotti18 In another study of neonatal hypertension, the prevalence was found to be 4.7% in NICUs. Reference Cowburn, Macias, Summers, Chilvers and Johnson19
In our study, the only contributing factor for the development of hypertension in the paediatric intensive care unit was the severity of multiple organ dysfunction, expressed by paediatric sequential organ failure assessment score. This is probably linked to the overactive sympathetic nervous system, which raises the risk of developing hypertension and cardiac remodelling. Reference Maggiore, Lellouche and Pignataro20
The respiratory diagnosis was a predictor of systemic hypertension in the paediatric intensive care unit. Maggiore et al. Reference Dunser and Hasibeder21 reported that excessive suction is associated with many adverse effects, including high blood pressure. The dynamic involvement of oxygen sensors found in peripheral tissue, which directly alters the cardiovascular response to the effects of hypoxia, is a different theory. Critical illness is characterised by sympathetic nervous system stimulation that may on some occasions exceed its beneficial effects, which may affect several organ systems. The heart appears to be one organ that is susceptible to sympathetic overshooting. Reference Tank and Lee Wong22 According to Tank et al., Reference Li, Gu, Sinha and Chowienczyk23 sustained elevation of circulating catecholamines for a prolonged time can also produce pathological conditions, such as cardiac hypertrophy and hypertension. This may explain why children with a longer duration of stay were more susceptible to hypertension.
In this study, critical children with acquired blood pressure elevation had a higher cardiac index and systemic vascular resistance index than the control group. Excess sympathetic stimulation may be a key mechanism in the pathophysiology of that type of hypertension.
According to Ye Li et al.’s Reference Gupta-Malhotra, Hamzeh, Poffenbarger, McNiece-Redwine and Hashmi24 investigation of the pathophysiology of hypertensive children, higher heart rate and cardiac output, rather than increased systemic vascular resistance, are better explanations for systemic hypertension in young patients. Cardiac performance was higher in hypertensive children, as expressed by myocardial performance index of the left ventricle. The isovolumetric contraction time increases because the left ventricle needs more time to overcome high systemic blood pressure to open the aortic valve. Gupta-Malhotra et al. Reference Lande, Meagher, Fisher, Belani, Wang and Rashid25 reported that in children with hypertension, myocardial performance index of the left ventricle was associated with increased mean systolic blood pressure.
Higher left ventricular mass index was found in the hypertensive group, a finding that correlates with Lande et al., Reference Kavey26 who found higher left ventricular mass index in children with transient white coat hypertension. Similar results were also demonstrated by Kavey, Reference Tran, Ehrmann and Messer27 who discovered that children and teenagers with systemic hypertension have higher left ventricular mass index.
Based on these results, we suggest that the use of beta-blockers is a suitable pathophysiological option for the treatment of children with paediatric intensive care unit-acquired hypertension.
The duration of stay was longer in the paediatric intensive care unit-acquired hypertension group than the non-hypertension group. According to Tran Cl et al., Reference Brady, Fivush, Flynn and Parekh28 about 1% of hospital discharges in the USA are associated with hypertension and with a longer hospital stay. The relation between hypertension and longer hospital stay may be related to those children’s higher severity of illness from the start.
Conclusion
Cardiac index, vascular resistance, myocardial performance, and left ventricle mass index increased in critically ill children with paediatric intensive care unit-acquired hypertension. The choice of antihypertensive medication needs to be influenced by each individual patient’s haemodynamics.
Limitations
We referenced left ventricular mass in relation to body surface area as most of our patients were not obese; however, indexing left ventricular mass by lean body mass needs to be considered in future studies. The methods used in this study to assess left ventricular dysfunction are limited by the effects of some parameters including left ventricular relaxation and atrial filling pressure. The technique, tissue Doppler imaging, could have also been used for a more accurate evaluation of diastolic dysfunction as the pulsed wave Doppler still needs validation in critical paediatric patients.
Acknowledgements
We would like to thank our nurses and patients without them, nothing would be completed.
Financial support
This research received no specific grant from any funding agency, commercial, or not-for-profit sectors.
Competing interest
None.
Ethical standards
The study was approved by the Ethical Committee of Cairo University.
