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Introduction

Advances in medical care have resulted in a shift in patient characteristics in our pediatric intensive care unit (PICU). We offer more specialized, complex care, tailored to the patient’s needs. This is facilitated by novel research that is focused on the pediatric population, competing with dogmas that sometimes are a result of the, often necessary, adaptation of evidence-based practice in adult intensive care patients to children. Nowadays, we thankfully have more guidelines that are based on recent research in a pediatric cohort of patients, leading to improved specialized therapy for critically ill children.

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What’s new in pediatric ventilation

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What’s new in pediatric cardiac intensive care?

Congenital heart disease is the primary indication for admission to the pediatric cardiac intensive care. Pediatric cardiac intensive care is a challenging discipline requiring collaboration between the pediatric cardiologist, the cardiac surgeon, the pediatric anesthesiologist and the pediatric intensivist. This partnership, facilitated by specialized technologies (Near Infrared Spectroscopy, Echocardiography) and novel pharmacotherapies (milrinone, inhaled nitric oxide (iNO)) has resulted in improved outcomes. Furthermore, the evolution of invasive catheterization techniques has made a hybrid approach more popular, with the goal to reduce the invasiveness of some procedures and delaying the need of major surgery.

Children admitted for both surgical or medical reasons to the PICU frequently suffer from hemodynamic instability. Early recognition and management is crucial. To aid our clinical practice, the European Society of Pediatric and Neonatal Intensive Care (ESPNIC) published the first recommendations for hemodynamic monitoring in critically ill children in 2020 [ ]. Fluid resuscitation is a common therapy, but predicting fluid responsiveness remains a challenge, as static parameters are known to be unreliable and dynamic parameters are still in need of further validation [ ]. In ventilated children, respiratory variation in aortic blood flow peak velocity seems to be the most reliable indicator for predicting fluid responsiveness. In non-ventilated children and in general, the recommendation is to administer recurrent smaller fluid boluses (5–10 ml/kg) [ ].

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What’s new in pediatric sepsis?

Sepsis is still a leading cause of morbidity and mortality for children worldwide. The majority of children who die from sepsis suffer from refractory shock or multiple organ dysfunction (MODS). Mortality for children with sepsis ranges from 5% to as high as 50%, depending on severity of illness, risk factors and geographic location. Early identification and appropriate management are crucial to optimize outcomes for children with sepsis. The first definitions and criteria for sepsis, severe sepsis and septic shock were published after the International Pediatric Sepsis Conference held in 2005. They were adapted from the adult definitions with modifications made for physiology based on age [ ]. In 2016 new adult definitions and criteria were published (Sepsis-3), but up to now, there are no official new pediatric sepsis definitions. The definition of (adult) sepsis in 2023 was updated to a “life-threatening organ failure caused by the host’s inappropriate response”, and septic shock as “a subset of sepsis in which underlying circulatory, cellular, and metabolic abnormalities contribute to a greater risk of mortality than that posed by sepsis alone”. The previous definition of severe sepsis is no longer used. The pathophysiology of sepsis is a complicated process outside the scope of this manuscript. In summary the normal host response to an infection (bacteria, virus or fungus) is a pro-inflammatory response that is regulated and localized by a simultaneous anti-inflammatory response. Sepsis occurs when this response is dysregulated with a generalized pro-inflammatory cascade, which will lead to widespread tissue injury.

In 2020 the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM) published the “Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-associated Organ Dysfunction in Children” as a guidance for clinicians [ ]. Adults typically present with a warm and distributive shock but in children clinical appearance is commonly characterized by constricted peripheral systemic vasculature, resulting in cold peripheries and prolonged capillary refill time named “cold shock”. Low blood pressure is mostly a very late sign. Cardiac ultrasound should be performed to exclude myocardial dysfunction and to choose the right vasoactive agent. Epinephrine and norepinephrine are currently preferred over dopamine.

In septic shock initial fluid resuscitation should be done with isotonic crystalloid bolus of 10–20 ml/kg. To facilitate rapid IV fluid administration, clinicians should consider alternative methods of vascular access (intraosseous access or central venous access). Fluids should be titrated to clinical markers of cardiac output and discontinued if signs of fluid overload develop. Initiating vasopressin or further titrating catecholamines can be done in patients who require high-dose catecholamines. The use of an inodilator can be considered if cardiac dysfunction persists. If possible, blood lactate levels should be monitored to aid resuscitation. Antimicrobial therapy should be started as soon as possible, within 1 h of recognition of possible sepsis; and preferably after obtaining blood cultures. The initial choice of empiric antimicrobials should take the specific clinical history and age into account. There is no current consensus on the use of IV hydrocortisone as an additional therapy for pediatric septic shock. In the adult population the addition of fludrocortisone to hydrocortisone is still debated [ ]. A recent large retrospective cohort study comparing hydrocortisone alone with hydrocortisone and fludrocortisone showed lower mortality in the hydrocortisone-fludrocortisone group [ ]. There is an unmet need for well conducted randomized clinical trials in the adult and pediatric population in this field of research. MODS in critically ill children is associated with high morbidity and mortality [ ]. The reliable identification of patients with MODS in children is of importance and the right scoring system is under debate. Commonly used descriptive scores are the Pediatric Logistic Organ Dysfunction Score-2 (PELOD-2) and the pediatric Sequential Organ Failure Assessment (pSOFA). Finally, VA-ECMO can be considered as a rescue therapy in children with refractory shock [ ].

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New insights on sedation and analgesia practices

Critically ill infants and children are exposed to a range of painful and stressful events during their stay in the PICU. Because these events are usually treated with analgesics and sedatives, administration of these agents is considered routine practice.Pain, agitation and delirium are a widely studied topic in adult critical care; Reade et al. introduced the concept of the ICU triad and stated that pain, agitation and delirium are inextricably linked to each other and so is their management [ ]. Unrelieved pain has adverse physical and psychological consequences evoking a stress response and may contribute to pulmonary complications in postoperative patients. Critically ill children should first receive adequate analgesia regardless of their need for sedation. The first consensus guidelines on sedation and analgesia in critically ill children were published in 2006 by the UK Pediatric Intensive Care Society [ ]. The ESPNIC published clinical recommendations in 2016 [ ]. In 2022 the SCCM published The Pain, Agitation, Neuromuscular Blockade, and Delirium in critically ill pediatric patients with consideration of the PICU Environment and Early Mobility (PANDEM) guideline [ ].

Pain assessment in infants and children can be challenging. The gold standard of pain assessment is self-report and can be used from 6 years old. Visual Analog Scale (VAS) or Numeric Rating Scale (NRS) are most frequently used. For children under the age of 6 years or nonverbal children, an observational rating scale is used. The Faces, Legs, Activity, Cry and Consolability (FLACC) or the COMFORT-Behavior (COMFORT-B) scale are both validated to assess pain and distress in critically ill children. Involving parents in pain assessment is a topic for further research. The management of pain in critically ill children involves both nonpharmacological as well as pharmacological agents. Environmental factors (temperature, noise), relaxation, distraction and facilitating sleep have a significant impact on comfort. Furthermore, the use of nonnutritive sucking with oral sucrose prior to performing (non-) invasive procedures in neonates and infants (<12 months old) is a well-known fact. Opioids remain the analgesic of choice for treating acute surgical and medical pain in critically ill pediatric patients, including pain associated with mechanical ventilation. Morphine and Fentanyl are the two most commonly used opioids worldwide. Knowledge of the pharmacokinetics and pharmacodynamics of the agent of choice and adaptation to age and critical illness is necessary. The use of adjunct nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen in the immediate postoperative period is associated with r educed pain scores and opioid consumption without increase in adverse events [ ].

Critically ill children requiring mechanical ventilation will need to receive sedation to reduce anxiety and to support ventilation. Setting the target depth of sedation and finding the right balance between over- and undersedation is paramount. Undersedation will lead to inadvertent device removal and increased anxiety. Oversedation is associated with prolonged mechanical ventilation, delirium, prolonged PICU length of stay and the development of tolerance and iatrogenic withdrawal. The ideal depth of sedation is based on the disease process and the child’s ability to cooperate with treatment. Assessment of depth of sedation and protocolized sedation is recommended. The Comfort-B scale or the State Behavior Scale (SBS) are both validated and reliable to use. Benzodiazepines are still widely used as a primary sedative agent, but are known to be associated with delirium and drug withdrawal [ ]. As an alternative, Dexmedetomidine, an alfa-2 agonist, proved to be safe as a primary sedative agent in a small multicenter RCT, is now recommended as a primary sedative agent in the postoperative patient with expected early extubation [ ]. If needed, midazolam can be given as a rescue, but its use should be limited. The use of continuous infusion of propofol is limited to avoid propofol infusion syndrome (PRIS), but it can be safely used at low doses (<4 mg/kg/h) for a short period (<48h) and may be a good alternative in the peri-extubation period when weaning other analgo-sedative agents. Ketamine, an NMDA antagonist, should only be considered in patients where optimal sedation depth is difficult to reach.

Inhalational anesthesia in the PICU is not routinely used or recommended but is possible with a standard mechanical ventilator used at the PICU. The most common used medical device for administration of inhalational anesthesia is the Sedaconda device. The main barrier to its use is the increase in dead space (50 ml) and the minimal tidal volume of 200 ml in a ‘typical’ setup. When installed on the inspiratory limb of the ventilator circuit, Sedaconda can potentially be used with tidal volumes as low as 30 ml. Both the use of sevoflurane and isoflurane with Sedaconda in the pediatric critically ill patient is currently under investigation. Given the intrinsic properties of volatile anesthetics, potential clinical benefits could be expected in patients with status epilepticus or status asthmaticus, with a decrease in length of ventilation.

The development of dependence, tolerance and iatrogenic withdrawal syndrome (IWS) are common complications after long-term sedation. IWS is well documented for opioids and benzodiazepines. Symptoms include central neurologic signs (irritability, delirium, seizures, hallucinations, mydriasis), gastrointestinal manifestations (feeding intolerance, diarrhea) and the activation of the sympathetic nervous system (tachycardia, hypertension, tachypnea, sweating, fever). After 5 or more days of continuous analgesia of sedative therapy, IWS occurs in 10–57% of patients. The Sophia Observation withdrawal Symptoms Scale and the Withdrawal Assessment Tool version-1 (WAT-1) are both validated to screen for IWS. Opioid related IWS and benzodiazepines IWS should be treated with opioid and benzodiazepines replacement respectively [ ]. Pediatric delirium is another common complication of long-term sedation. It occurs in more than 20% patients. The pathophysiology of delirium remains incompletely understood; it’s a complex interplay of predisposing and precipitating factors. Three subtypes of pediatric delirium exist; namely hyperactive, hypoactive and mixed delirium. Hypoactive delirium is the most frequent subtype in children. Routine screening for delirium is recommended and can be done with the pediatric Confusion Assessment Methods for the ICU (p-CAM-ICU) or the Cornell Assessment for Pediatric Delirium. The routine use of haloperidol or atypical antipsychotics is not recommended, but should be considered in patients with refractory delirium [ ].

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New insights on nutrition in the PICU

Critically ill children are often unable to receive full oral feeding. Major limiting factors are mechanical ventilation, muscle weakness or intrinsic gastrointestinal related factors (gastroparesis, ileus or swallowing disorders) . Consequently, a pronounced macronutrient deficit develops within a few days. A nasogastric feeding tube is often inserted to allow initiation of enteral feeding as soon as possible. Assuming that nutritional intake in children should not only equal basic metabolic needs, but should also allow children to grow, optimum targets for macronutrient delivery are deemed to be higher than for adults [ ]. Unfortunately, achieving growth during critical illnesses is highly unlikely. At admission, nutritional assessment and screening for malnutrition can be done with the Screening Tool for Risk of Impaired Nutritional Status and Growth (STRONGKids) [ ]. It remains unclear whether patients with malnutrition are more likely to benefit or experience harm from earlier or enhanced nutrition support. Protocol – based nutritional support in PICU is recommended. Several guidelines have been developed with the ESPNIC, the European Society for Clinical Nutrition and Metabolism (ESPEN) and the American Society for Clinical nutrition and Metabolism (ASPEN) being the most widely adopted [ , ].Critical illness induces profound metabolic and endocrine changes characterized by catabolism , insulin resistance and shifts in substrate utilization. As the metabolic and endocrine response evolves over the course of critical illness, nutritional support may also need to be tailored to the different phases of critical illness, where the physiologic anorexia of severe illness might be initially adaptive but detrimental when it is tolerated for more than a week. Withholding parenteral nutrition for up to one week, while providing adequate doses of micronutrients, prevented morbidity and promoted recovery in the largest international multicenter nutrition RCT in children, the PEPaNIC RCT, independent of nutritional status [ ]. Parenteral glucose provision should be sufficient to avoid hypoglycemia. It is recommended to start enteral nutrition within 24h–48h after admission and to increase stepwise until the feeding goal is achieved using a feeding protocol. The optimal feeding volume and timing to improve outcomes in critically ill children remains debated as is the case in the adult population. Hyperglycemia is prevalent in critically ill children and the extent of hyperglycemia correlates with risk of organ failure, length of stay and mortality [ ]. Normal fasting values for blood glucose concentrations in infants and children are lower than in adults. Tight glucose control (80–110 mg/dl) with insulin treatment has emerged as possible strategy to improve outcome, but the current evidence is conflicting [ ]. Therefore, when considering tight glucose control in pediatric critically ill patients, the possible harm of hypoglycemia should be balanced against potential benefit, taking into account the adequacy of glucose monitoring. Brief episodes of hypoglycemia do not appear to increase mortality, neither do they worse neurocognitive performance when compared with critically ill children not experiencing hypoglycemia [ ]. Continuous glucose monitoring is advisable and the prevention of excessive hyperglycemia (>215 mg/dl, the renal threshold) is undoubtedly recommended.

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What’s new in POCUS in the PICU

Ultrasound has already proven its usefulness in the PICU, for example as a tool to diagnose pneumonia, evaluate fluid balance, diagnose cardiac tamponade and screen for vocal cord dysfunction [ ]. However, it currently still lags behind several other implemented technologies, lacking a standardized training and certification process and wide variation in competency, application and protocols used across our units. Several areas in pediatric critical care will benefit even more from this technology as new studies and protocols are rapidly developed , as summarized below.

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Long term impact of pediatric critical illness

Survival of critical illness has improved over time, with mortality rates below 5% in modern PICUs. Unfortunately, many patients endure devastating long-term effects after critical illness including cognitive impairment [ ]. In adult critical care, this is a well-known part of the Post Intensive Care Syndrome (PICS), which is receiving increasing attention. Critical illness in children is associated with impaired physical, neurocognitive, emotional and behavioral development [ , ]. Consequently, research efforts are shifting from short-term vital outcomes to long-term morbidity and quality-of-life after PICU discharge. Not only pre-admission related factors (psychosocial environmental factors) and disease-related factors (e.g. cardiac arrest, brain injury) are important, medical management is of utmost importance to avoid additional harm [ ]. Anesthetic and analgesic drugs have shown harm in preclinical studies, although in humans with short exposure of anesthesia this was not reproducible [ ]. However , avoiding unnecessary exposure to anesthetic and analgesic agents is essential. The search is on for other possible avoidable intensive care-related factors contributing to these detrimental outcomes. Hyperglycemia, phthalates leaching into the blood from indwelling medical devices and refraining from early use of parenteral nutrition seem to be of importance [ ]. Because of the awareness of adverse neurocognitive outcome after pediatric critical illness, research interest in this field has increased with hopeful novel insights [ ]. Follow-up is now mainly within research projects but the question remains whether follow-up should be standardized after prolonged critical illness.

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Family centered care

As part of the Assessing Pain, Both Spontaneous Awakening and Breathing trials, Choice of Sedation, Delirium Monitoring/Management, Early Exercise/Mobility and Family Engagement/Empowerment (ABCDEF) bundle [ ], family centered care lies at the heart of the care for critically ill children [ ]. Family engagement and empowerment have potential beneficial effects on long term sequelae. In a recent survey, 88% of all respondents indicated that family engagement was implemented in their unit. Jones et al. recently demonstrated the effectiveness of a ‘glass-door’ daily goals communication tool to improve family engagement [ ]. This project used a visible sheet that was put on the front of each patient room to improve patient team collaboration and communication. The intervention was well received among patients’ families, with 66% of parents finding it helpful to understand the daily goals for the patient and boosting family engagement. A similar result was seen in a PICU in Montréal [ ]. An additional tool explored was the use of an ICU diary completed by parents, along with nurses, physicians and other health care providers. When asked, both parents and health care staff had a positive perception of this PICU diary [ ], which helped in parent-caregiver communications.

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Summary

As PICUs provide more specialized and complex care, the need for specific guidelines and research to improve and tailor our patient care is increasing. In the last few years, several landmark papers have been published, and pediatric critical care societies have pioneered collaboration across different fields of interest, including mechanical ventilation, cardiac critical care, sepsis, sedation and pain management, family centered care, muscle function testing and nutrition. We have provided a summary of some of these recent advancements.

Practice points

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  High flow nasal oxygen therapy has different effects on the respiratory system compared to CPAP: it is preferred when secretion clearance is important and when a low amount of PEEP and modest help with work of breathing is needed

  
  
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  CPAP should be considered as a first-line therapy in the setting of respiratory insufficiency after ventilator liberation and extubation

  
  
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  In case of massive bleeding the use of viscoelastic tests is recommended

  
  
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  Protocolized sedation, with attention for delirium and iatrogenic withdrawal syndrome is considered to be standard-of-care

  
  
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  Ultrasound is further expanding its use as a point-of care tool in the PICU, with now also a potential use f or monitoring muscle weakness

  
  
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  Up-to-date medical management to avoid additional harm to PICU survivors is paramount

Research agenda

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  The role and potential risks of the use of noninvasive ventilation in pediatric ARDS need to be further defined

  
  
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  The use of viscoelastic tests in children should be further explored with defining of correct reference ranges

  
  
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  Long-term follow-up of children with Left Ventricular Assist Device should be done with attention for safety of Novel Oral Anticoagulants (NOAC)

  
  
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  The use of IV corticosteroids as an adjunctive therapy for septic shock should be further investigated in well conducted randomized clinical trials in children

  
  
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  The use of inhaled sedation in the PICU should be further explored

  
  
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  Strategies to detail and prevent respiratory muscle dysfunction during mechanical ventilation are not well known in the PICU cohort

  
  
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  The search for possible intensive care-related factors contributing to long-term morbidity after survival of critical illness is important

Financial support

Tom Schepens received a grant from the Research Foundation Flanders ( FWO-TBM T004620 N ).

CRediT authorship contribution statement

R. Haghedooren: Conceptualization. T. Schepens: Conceptualization.