Vera Saldien

Background: In the paediatric intensive care unit (PICU), certain drugs should be avoided or administered with strict precautions and close monitoring. This is due to their potential for toxicity or adverse effects or a lack of safety data, especially for critically ill children with organ failure. Additionally, practitioners must assess the unique pharmacokinetic and pharmacodynamic properties of drugs when treating critically ill children. In this narrative review, we highlight the risks, advantages, and disadvantages of three exemplary cases of drugs for paediatric patients hospitalised in the PICU: chloramphenicol, acetylsalicylic acid, and propofol. Methods: Apart from key papers on these drugs, a retrospective analysis of the English literature on chloramphenicol, acetylsalicylic acid (ASA), and propofol was performed on PubMed for papers from January 2014 to December 2025. Results: Chloramphenicol should be avoided in neonates due to the risk of grey baby syndrome. Acetylsalicylic acid (ASA) is contraindicated in children ≤18 years with suspected viral illness because of the risk of Reye’s syndrome, but remains essential for Kawasaki disease and post-cardiac surgery antiplatelet therapy. Propofol should be avoided when used for a longer period at high doses. With proper dosing and monitoring, propofol-related infusion syndrome (PRIS) is preventable, but high-risk patients should receive alternative treatment. Conclusions: This narrative review highlights the significant risks associated with the use of chloramphenicol, ASA, and propofol in paediatric intensive care settings. Their potential for life-threatening and severe adverse reactions emphasises the need for cautious and informed use. Clinicians must carefully consider the risks and benefits of these drugs. To minimise adverse events, strict monitoring, dose adjustments, and the use of safer alternatives are essential. However, it appears that their use in well-defined circumstances in acute illness in children is still warranted. The findings of this narrative review underscore the need for further research to focus on identifying high-risk biomarkers, genetic predispositions, and safer alternatives to improve evidence-based guidelines and reduce morbidity and mortality in paediatric intensive care.

Background/Objectives: Cancer’s complexity can be rationalized through the “hallmarks of cancer,” which define the key biological capabilities driving malignancy. Induced hyperthermia—an adjunctive therapy that elevates body temperature above the normal setpoint for a defined period—has been explored for its modulatory effects on these hallmarks. This systematic review aims to evaluate the effects and mechanisms of induced hyperthermia on tumor cells through the established hallmarks of cancer framework. Methods: A systematic search following the Cochrane guidelines and PRISMA assessment tool was conducted in PubMed and Cochrane Library (2000–2025) to identify reviews on the effects of induced hyperthermia on cancer hallmarks. Studies’ predefined inclusion criteria were independently evaluated by two external teams and graded using PRISMA standards. Results: From the 2015 records screened, 103 studies met the inclusion criteria. Evidence indicates that induced hyperthermia modulates seven of the ten cancer hallmarks. The most well-supported mechanisms of action include (1) the immune system activation (39–41 °C)—enhancing antigen presentation, activating innate/adaptive immune cells, promoting tumor infiltration—and (2) genome instability and mutation (41 °C)—impairing DNA repair pathways and increasing tumor vulnerability. Both hallmarks provide evidence clarifying the mechanistic pathways through which induced hyperthermia exerts its effects. Conclusions: Induced hyperthermia exerts multifaceted, temperature-dependent effects on cancer biology, predominantly through immune activation and genomic destabilization. While it enhances the therapeutic sensitivity of other treatment modalities (e.g., chemotherapy, radiotherapy) and antitumor responses, excessive heating may induce immune suppression and thermotolerance. Optimizing temperature parameters and identifying biomarkers are essential for integrating hyperthermia into targeted and multimodal cancer therapies.

Neuromuscular blocking agents (NMBAs) are critical components in paediatric anaesthesia, facilitating intubation, surgical procedures and mechanical ventilation in neonates, infants and children. This narrative review examines the pharmacological properties, clinical applications, monitoring, reversal and safety of NMBAs across paediatric populations. Given the unique physiological characteristics of neonates and infants – including hepatic and renal maturation, and neuromuscular junction development – NMBA metabolism, efficacy and adverse effects in these age groups differ markedly from those in older children and adults. These physiological factors necessitate specific approaches to NMBA selection, dosing and monitoring to ensure effective blockade while minimising risks. Emphasis is placed on understanding how the pharmacokinetics and pharmacodynamics of commonly used NMBAs vary with age, influencing onset, duration and recovery. Additionally, practical strategies for the safe and effective monitoring of neuromuscular blockade using quantitative monitoring techniques are discussed to avoid residual neuromuscular blockade. Recent advances in the reversal of neuromuscular blockade, including the use of sugammadex, offer promising improvements in paediatric anaesthesia safety, though their application in neonatal populations requires further study. Finally, the review discusses current research trends, highlighting the need for age-specific guidelines and pharmacologic innovations that address the challenges unique to NMBA use in neonates, infants, and children.

Background: Sugammadex is well tolerated and effective for reversing neuromuscular blockade (NMB) in adults and children as young as 2 yr old. There is little information on its use in younger children. The aim of this study was to evaluate the efficacy and tolerability of sugammadex in children under 2 yr of age. Methods: This was a phase IV, randomized, parallel-group, multicenter clinical trial of sugammadex in participants aged birth to less than 2 yr (NCT03909165). Part A was open label and included pharmacokinetic assessments to determine whether sugammadex dose adjustment for part B was necessary based on age. Part B was double-blind and evaluated doses of 2 and 4 mg/kg sugammadex. Participants were randomized to (1) moderate NMB and reversal with 2 mg/kg sugammadex; (2) moderate NMB and reversal with neostigmine + glycopyrrolate or atropine (hereafter, called neostigmine); or (3) deep NMB and reversal with 4 mg/kg sugammadex. The primary efficacy endpoint was time to neuromuscular recovery (TTNMR). The primary efficacy hypothesis was that 2 mg/kg sugammadex would be superior to neostigmine for the reversal of moderate NMB as measured by TTNMR in part B. Results: A total of 138 participants aged 1 to 720 days were treated in parts A and B (2 mg/kg sugammadex, n = 44; 4 mg/kg sugammadex, n = 63; and neostigmine, n = 31). Based on pharmacokinetic assessments in part A, no dose adjustments for age were needed. In part B, TTNMR for reversal of moderate NMB was faster with 2 mg/kg sugammadex than neostigmine (median of 1.4 min vs. 4.4 min; hazard ratio, 2.40; 95% CI, 1.37 to 4.18; P = 0.0002). A 4-mg/kg dose of sugammadex achieved rapid TTNMR for reversal of deep NMB with a median of 1.1 min (parts A and B). The percentage of participants with one or more adverse events (parts A and B) was similar for sugammadex and neostigmine. No deaths, drug-related serious adverse events, or hypersensitivity or anaphylaxis events were reported. Conclusions: In children less than 2 yr old, 2 mg/kg sugammadex reversed moderate NMB faster than neostigmine, and 4 mg/kg sugammadex rapidly reversed deep NMB. Sugammadex doses of 2 and 4 mg/kg were well tolerated.

Introduction: The abscopal effect is a systemic immune response characterized by metastases regression at sites distant from the irradiated lesion. This systematic review aims to explore the immunological mechanisms of action underlying the abscopal effect and to investigate how hyperthermia (HT) can increase the chances of radiotherapy (RT) triggering systemic anti-tumor immune responses. Methods: This review is created in accordance with the PRISMA guidelines. Results and Conclusion: HT and RT have both complementary and synergistic immunological effects. Both methods trigger danger signal release, promoting cytokine and chemokine secretion, which increases T-cell infiltration and facilitates cell death. Both treatments upregulate extracellular tumor HSP70, which could amplify DAMP recognition by macrophages and DCs, leading to stronger tumor antigen presentation and CTL-mediated immune responses. Additionally, the combined increase in cell adhesion molecules (VCAM-1, ICAM-1, E-selectin, L-selectin) could enhance leukocyte adhesion to tumors, improving lymphocyte trafficking and boosting systemic anti-tumor effects. Lastly, HT causes vasodilation and improves blood flow, which might exacerbate those distant effects. We suggest the combination of local radiotherapy with fever-range whole-body hyperthermia to optimally enhance the chances of triggering the abscopal effect mediated by the immune system.

Background: The use of neostigmine after neuromuscular blockade (NMB) has been associated with postoperative respiratory complications. In previous studies, we found lower diaphragmatic activity after neostigmine reversal of NMB, compared to sugammadex. It is still unclear whether the adequate use of neostigmine guarantees normal respiratory muscle function after NMB. In this study, we wanted to assess the effect of commonly used degrees of NMB and their possible reversal strategies on respiratory muscle activity after the return of normal neuromuscular transmission. Methods: This is a randomized, controlled, parallel-group, single-centre, double-blind study in patients scheduled for intracranial surgery at a tertiary academic hospital in Belgium. All participants received target controlled propofol/remifentanil anesthesia and were randomized into one of five groups, receiving either a shallow NMB with no reversal (shallow/saline), a shallow NMB with sugammadex reversal (shallow/sugammadex), a moderate NMB with neostigmine reversal (moderate/neostigmine), a moderate NMB with sugammadex reversal (moderate/sugammadex), or a deep NMB with sugammadex reversal (deep/sugammadex). Primary and secondary outcome parameters were diaphragm and intercostal electromyographic (EMG) activity at the moment of resumed spontaneous breathing activity, defined as a maximal interval of 10 min after the first spontaneous breath. Results: For the five groups, a total of 55 patients could be included in the final analysis. Median time of spontaneous breathing analyzed was 5 min (IQR 3–9.5 min). Both the moderate/sugammadex and the moderate/neostigmine groups had lower levels of diaphragm EMG compared to the shallow/sugammadex group. The moderate/neostigmine group had lower levels of intercostal EMG activity compared to the shallow/saline group. Conclusions: In this study, the depth of neuromuscular blockade and type of reversal strategy impacts respiratory muscle activity at the moment of resumed spontaneous breathing and recovery of neuromuscular blockade. Both groups that received moderate NMB had lower levels of diaphragm EMG, compared to the shallow NMB group with sugammadex reversal. Compared to the shallow NMB group with no reversal, the moderate NMB with neostigmine reversal group had lower intercostal EMG activity. Trial registration: Clinicaltrials.gov NCT01962298 on October 9, 2013 and EudraCT 2013–001926-25 on October 10, 2013.

Spine surgery is associated with considerable postoperative pain and can be challenging to treat. A loco-regional technique suitable for spine surgery should cover the dorsal root of the spinal nerves at the levels where surgery is performed. The erector spinae block is a loco-regional technique with promising results and was recently described at the thoracic level. There are no randomized trials of this technique on a lumbar level. This study tests the hypothesis that the 24-h postoperative morphine consumption is significantly lower in patients undergoing posterior lumbar inter-body fusion surgery with a lumbar erector spinae (LUMBES) block when compared with a sham block. This prospective randomized double-blind multicenter study will randomly allocate 80 adult patients undergoing elective posterior lumbar inter-body fusion surgery during general anesthesia to one of two groups as follows: (1) bilateral erector spinae block (20 mL 0.25% levobupivacaine) or (2) bilateral sham block (20 mL NaCl 0.9%). Our primary endpoint is 24-h postoperative morphine consumption. Secondary endpoints include 72-h morphine consumption, intraoperative sufentanil dosage, postoperative pain scores at regular time intervals both at rest and during movement, time to first postoperative mobilization, and the Quality of Recovery 40 survey score. The LUMBES trial is a pragmatic clinical study that will provide evidence of whether a bilateral lumbar erector spinae block is effective in reducing 24-h postoperative morphine consumption in patients undergoing lumbar inter-body fusion surgery. If this hypothesis is confirmed, this finding could contribute to more widespread implementation of this technique. Local ethics committee B300201837508, ClinicalTrials.gov identifier: NCT03825198 . Registered on 31 Jan 2019.

Target-controlled infusion (TCI) of rocuronium can be used to maintain a stable blood concentration (Cp). At steady-state, the pharmacokinetics (PK) are compensated for by TCI, and a stable effect can be observed. The theoretical Cp may represent effect-site concentration (EC). We used the EC-effect relationship to study pharmacodynamics (PD) in infants, children, and adults. After giving their written, informed consent, 14 infants, 23 children, and 21 adults scheduled for elective surgical procedures received 3 to 6 ascending Cp targets of TCI rocuronium according to PD data. Just before each increase of TCI, venous blood samples were taken to measure Cp. Neuromuscular block was evaluated acceleromyographically. Individual effect data and measured Cp were fitted to the Hill equation. Maximum block during TCI targets—1000, 1300, and 1600 ng/mL—was smaller in children in comparison with infants and adults. The concentration in the effect compartment associated with a 50% drug effect (EC50) was significantly smaller in infants (mean [sd]) (652 [215] ng/mL) than in adults (954 [276] ng/mL) and was the largest in children (1200 [295] ng/mL). Calculated mean EC90 values were 1705, 2230, and 2035 ng/mL, respectively, in infants, children, and adults. TCI rocuronium established steady-state PK/PD at different TCI targets and allowed us to define PK/PD relationships in a standardized way. Steady-state TCI rocuronium revealed the most potency of rocuronium in infants and the least in children.