Hemodynamic effects of intravenous paracetamol in critically ill children with septic shock on inotropic support

Abstract

Background: Treatment with intravenous paracetamol may impair hemodynamics in critically ill adults. Few data are available in children. The aim of this study was to investigate the frequency, extent, and risk factors of hypotension following intravenous paracetamol administration in children with septic shock on inotropic support. Methods: We retrospectively reviewed the electronic medical charts of all children aged 1 month to 18 years with septic shock who were treated with intravenous paracetamol while on inotropic support at the critical care unit of a tertiary pediatric medical center in 2013-2018. Data were collected on patient demographics, underlying disease, Pediatric Logistic Organ Dysfunction (PELOD) score, hemodynamic parameters before and up to 120 min after paracetamol administration, and need for inotropic support or intravenous fluid bolus. The main outcome measures were a change in blood pressure, hypotension, and hypotension requiring intervention. Results: The cohort included 45 children of mean age 8.9 ± 5.1 years. The mean inotropic support score was 12.1 ± 9.5. A total of 105 doses of paracetamol were administered. The lowest mean systolic pressure (108 ± 15 mmHg) was recorded at 60 min (p = 0.002). Systolic blood pressure decreased at 30, 60, 90, and 120 min after delivery of 50, 67, 61, and 59 drug doses, respectively. There were 5 events of systolic hypotension (decrease of 1 to 16 mmHg below systolic blood pressure hypotensive value). Mean arterial pressure decreased by ≥ 15% in 8 drug doses at 30 min (7.6%, mean − 19 ± 4 mmHg), 18 doses at 60 min (17.1%, mean − 20 ± 7 mmHg), 16 doses at 90 min (15.2%, mean − 20 ± 5 mmHg), and 17 doses at 120 min (16.2%, mean − 19 ± 5 mmHg). Mean arterial hypotension occurred at the respective time points in 2, 13, 10, and 9 drug doses. After 12 drug doses (11.4%), patients required an inotropic dose increment or fluid bolus. Conclusions: Hypotensive events are not uncommon in critically ill children on inotropic support treated with intravenous paracetamol, and physicians should be alert to their occurrence and the need for intervention.

A narrative review of paracetamol‐induced hypotension: Keeping the patient safe

“…The authors suggested that IV paracetamol administration in critically ill children in septic shock, who also require inotropic support, can exacerbate hypotension. The authors cautioned clinicians on the need for timely intervention of any resultant untoward haemodynamic manifestation (Nahum et al., 2020).…”

“…The authors concluded that IV paracetamol provided pain relief and therefore enhanced a reductive effect on both HR and BP without haemodynamic compromise (Nahum et al., 2019). Following this chart review, Nahum et al., (2020) performed a retrospective observational study, which explored the haemodynamic effect of IV paracetamol administration in paediatric patients who were admitted to the critical care unit with septic shock and who also received inotropic support (Nahum et al., 2020). The study indicated that IV paracetamol administration caused significant mean arterial hypotension in 32.4% of recipients.…”

“…The authors cautioned clinicians on the need for timely intervention of any resultant untoward haemodynamic manifestation (Nahum et al, 2020).…”

Fever: Could A Cardinal Sign of COVID-19 Infection Reduce Mortality?

“…A key mechanism for lowering temperature is by initiation of cutaneous vasodilation, 50 , 51 , 52 similar to what occurs during defervescence, which facilitates arterial heat dissipation from the skin. This vasodilation can occur to varying degrees in a febrile patient, but studies in both adults 53 , 54 , 55 and children 56 , 57 have shown this often leads to a clinically significant fall in mean arterial pressure. The subsequent acetaminophen-induced hypotension is then countered with fluid and/or vasopressor support to maintain adequate organ perfusion.…”

“…The subsequent acetaminophen-induced hypotension is then countered with fluid and/or vasopressor support to maintain adequate organ perfusion. [53][54][55][56][57] Thus, a vicious cycle ensues as we desperately work against the normal physiology of the body to maintain blood pressure, but as total body water stores increase, oxygenation in the lungs then becomes compromised, inducing unnecessary harm. 58 The time for an evidence-based approach to fluid management in the febrile patient is long overdue.…”