|Year : 2015 | Volume
| Issue : 4 | Page : 469-473
Sedation and analgesia after pediatric cardiac surgery
Mai M Abdel Aziz MD
Department of Anesthesia, Ain Shams University, Cairo, Egypt
|Date of Submission||05-Oct-2015|
|Date of Acceptance||09-Oct-2015|
|Date of Web Publication||29-Dec-2015|
Mai M Abdel Aziz
Department of Anesthesia, Ain Shams University, Cairo
Source of Support: None, Conflict of Interest: None
Sedation and analgesia following pediatric cardiac surgery is of paramount importance. Individualized sedation and analgesia strategies starting in the operative theater and continuing in the postoperative period need to be recognized as an important aspect of perioperative care. This aims toward speeding recovery, minimizing PICU length of stay, and avoiding the development of postsurgical stress syndrome. Patient-tailored protocols should be implemented based on validated pain/sedation scores. Understanding the pharmacological aspects and side effects of various sedative/analgesic drugs, as well as continuous dose adjustment according to follow-up scoring system and variable patient hemodynamic state and response, is mandatory.
Keywords: pain scores, pediatric cardiac surgery, pediatric intensive care unit, sedation, analgesia
|How to cite this article:|
Abdel Aziz MM. Sedation and analgesia after pediatric cardiac surgery
. Ain-Shams J Anaesthesiol 2015;8:469-73
In recent years, appropriate intraoperative anesthesia and analgesia during cardiac surgery has become recognized as an important factor in postoperative recovery. This includes early perioperative management of the neonate undergoing radical surgery and more recently the care surrounding fast-track and ultra-fast-track surgery. However, outside these areas, relatively little attention has been focused on postoperative sedation and analgesia within the pediatric intensive care unit (PICU). This reflects the perceived priorities of the primary disease process over the supporting structure of PICU, with a generic approach to sedation and analgesia that can result in additional morbidities and delayed recovery  .
Individualized sedation and analgesia strategies, starting in the operating theater and continuing through hospital discharge, need to be regarded as an important aspect of perioperative care to speed-up the process of recovery.
There are different contributors to anxiety and agitation in the PICU. There is a marked variability in patient type (age, weight, and comorbid conditions), procedure type, length of stay, the need for prolonged ventilation, or the need for minor procedures such as arterial cannulae or central venous cannulation. The pain or anxiety may further be magnified by psychological factors such as separation from the parent, disruption of the day-night cycle, and presence of unfamiliar individuals and machines  .
Physiological causes of agitation, such as hypoxemia, hypercapnia, and cerebral hypoperfusion, due to reduced cardiac output (COP), have to be excluded.
Pain and anxiety during the postoperative period have to be addressed judiciously. Inadequate analgesia and postsurgical stress response is a metabolic, humoral, and hemodynamic response following injury or surgery. This neuroendocrine cascade leads to increased oxygen consumption, increased carbon dioxide production, and a generalized catabolic state with a negative nitrogen balance. Recent studies have concluded that inadequate pain control causes long-term dysregulation of nociceptive mechanisms, which may change the behavior and responses to future pain stimuli  .
Sedation is a broad term that facilitates several goals, which include unconsciousness or reduction in consciousness level, reduced awareness, loss of explicit and implicit memory, compliance with the need to lie attached to monitors and invasive lines, and prevention of distress.
There can be significant individual variation. Assessment of the depth of sedation, with the titration of analgesic and sedative drugs, is important to ensure comfort and avoid adverse outcomes that are associated with undersedation or oversedation  .
Various scores have been implemented for the evaluation and follow-up of sedation in pediatric patients. Sedation level can be assessed using Ramsay sedation score, FLACC (Faces, Legs, Arms, Cry, and Consolability) score for pediatric population between the age 0 and 8 years, the COMFORT scale for intubated, nonparalyzed patients, sedation analgesia score, and visual analog score [Table 1] , .
The comfort scale is an objective measure of distress in ventilated pediatric patients, validated in all age groups. It comprises eight variables, each rated from 1 to 5: alertness, calmness or agitation, respiratory response, physical movement, heart rate, blood pressure, muscle tone, and facial tension. The scale ranges from 0 to 40, with a target range of 17-26. As with other scoring systems, it is limited by interobserver variability, provides only intermittent data, and cannot be used in the context of neuromuscular junction blockade.
The FLACC scale has been implemented as it is better suited for pediatric population as it involves physiological and/or behavioral measurements, including vital signs, body posture and movements, and facial expressions to indicate the level of pain that a patient may experience [Table 2] , .
No single scoring system is more effective than another, although some may be of limited use in paralyzed patients. These tools should be used upon initiation of therapy, continuously with maintenance therapy, and following dose adjustments.
Several tools have been developed to assess withdrawal symptoms following iatrogenic exposure to sedative agents and opioids. Examples of scoring tools include the Withdrawal Assessment Tool 1 (WAT-1) and the Lipsitz Tool  .
The choice of analgesic/sedative agent in PICU should take into consideration age-related pharmacokinetic and pharmacodynamic changes. There are significant variabilities in absorption, distribution, metabolism, and excretion within the first years of life. Neonates and infants have limited capability for metabolism through the liver including cytochrome P450 and glucuronidation enzymatic reaction. These pathways usually mature by 6 months of age. These pathways, for example, are responsible for the metabolism of morphine into its active metabolite morphine-6-glucoronide. The diminished metabolism may result in an apparent reduced efficacy.
Glomerular filtration rate and tubular secretion are diminished in neonates  . Medications or active metabolites that are renally excreted may require dose adjustment to prevent excessive accumulation.
The ideal agent to be used should classically have a rapid onset of action, predictable duration of activity, easy titration using continuous infusion, limited effect on cardiorespiratory function, wide therapeutic index, and no interference with the metabolism or effect of concomitantly administered drugs.
Misconceptions about pain recognition and management in children have resulted in suboptimal treatment outcomes  .
Pain scores used in PICU include the FACES pain rating scale, the numeric pain scale, and the Oucher scale. The WHO classifies pain as mild, moderate, and severe. Nonopioid analgesics are the mainstay for management of mild pain. Opioids can be combined with nonopioid analgesics for mild-to-moderate pain. Severe pain requires establishment of opioid schedule. Intermittent doses can be useful for breakthrough pain, although this strategy may result in fluctuations of plasma concentrations. As a result, patients with severe postoperative pain and those who are being treated with mechanical ventilation should receive patient-controlled analgesia (PCA) and opioid continuous infusion (CI), respectively.
| Nonopioid analgesics|| |
Most commonly used nonopioid analgesic agents include acetaminophen, NSAID, and sucrose. These agents demonstrate opioid-sparing effects but are inappropriate in moderate or severe pain because of their ceiling effect where in high doses the adverse effects outweigh the benefits. However, unlike opioid analgesics, these agents are not associated with respiratory depression, constipation, urinary retention, or withdrawal manifestations.
Acetaminophen is a centrally acting cyclo-oxygenase-3 inhibitor that, unlike NSAIDs, does not have anti-inflammatory effects. It is available in various formulations, including oral tablets, liquid preparations, and intravenous solutions. Children younger than 12 years old should receive a dose not exceeding 75 mg/kg/day orally  .
The most commonly used NSAIDs in PICU include ibuprofen and ketorolac. They exhibit analgesic and anti-inflammatory effects through inhibition of prostaglandin synthesis. However, their use may be limited in postcardiac surgery pain because of their effect on platelet aggregation and the increased risk of bleeding [Table 3]  .
| Opioid analgesic agents|| |
Opioid analgesic agents inhibit the transmission of nerve impulses through the ascending nerve pathways in the spinal cord and higher levels in the central nervous system by binding to opiate receptors. Intermittent intravenous doses may be effective for patients needing immediate postoperative pain relief but have been associated with inadequate pain control when plasma concentrations fall between subsequent doses.
Continuous infusion and PCA has been proven by various studies to provide a more consistent and effective pain management during the postoperative period. Studies have shown that PCA can be used in children as young as 6 years of age. This involves the implementation of five components: an initial dose, basal rate, PCA bolus dose, lockout time, and maximum opioid dose per hour or per every 4 h depending on the various institute policy  .
The most commonly used agents for continuous infusion or PCA are morphine, fentanyl, and hydromorphone. Morphine is the most frequently used agent. It is renally eliminated with a half-life of 1-3 h in infants and older children but with a half-life of up to 10 h in preterm patients. Moreover, in the postcardiac surgery setting, morphine may result in hypotension mediated through vasodilatation, histamine release, and a negative inotropic effect with a decrease in baroreceptor response. This is especially prominent in hemodynamically unstable patients. In such cases, fentanyl would be a more suitable alternative. As opposed to morphine, it does not result in histamine release, has a more rapid onset of action within 30 s, and a relatively short half-life of 2 h. [Table 4] shows the proposed opioid dosing in PICU  .
Continuous infusion of opioids is associated with increased dosage requirements. Therefore, dosage titration must be guided by appropriate sedation score, pain scales, and comfort scales.
Adverse effects reported with the use of opioids have to be taken into consideration and monitored, the most important being respiratory depression and apnea in nonventilated patients, especially in infants younger than 6 months of age, due to decreased renal elimination and hepatic immaturity. Other reported side effects include constipation, urinary retention, nausea/vomiting, and pruritus. The prolonged use of opioids may be associated with the development of tolerance, which is a decrease in the analgesic effect despite consistent serum drug concentration. This can be managed by increasing the opioid dose, shifting to other agents or adding another agent (e.g. ketamine)  .
Extended opioid use can also result in physiological dependence. Withdrawal manifestations present after discontinuation of opioids in the form of central nervous system irritability, sleep disturbance, autonomic dysfunction, and gastrointestinal dysfunction, a syndrome called iatrogenic opioid abstinence syndrome.
| Sedative agents|| |
Several sedative agents are available for use in PICU. These primarily include benzodiazepines, a2 agonists, propofol, and ketamine.
Benzodiazepines are GABA receptor agonists that provide sedation and anxiolysis. Despite having no analgesic effect, they have an opioid-sparing effect by modifying the perception of pain. Midazolam is the most commonly used agent in PICU. It is metabolized by CYP and requires dose adjustment in infants with renal impairment because of the presence of an active metabolite that is renally excreted. Diazepam is less commonly used in PICU due to its relatively longer half-life. It requires dose adjustment in infants with hepatic/renal disease  .
Benzodiazepines are highly effective in the PICU but they all can cause respiratory depression, which is dose dependent, and increases with the coadministration of other sedative/opioid agents. Flumazenil can be used to reverse this effect. Benzodiazepines may also produce hemodynamic effects by decreasing central sympathetic outflow and systemic vascular resistance, especially in children with cyanotic heart disease or hypovolemia. Careful dosing and meticulous monitoring is mandatory.
Drug withdrawal may occur following discontinuation of benzodiazepines, and, unlike opioid withdrawal, there are no gastrointestinal symptoms. Monitoring using assessment tools such as WAT-1 can assess withdrawal. Withdrawal manifestation can be managed by gradual tapering or substitution with an enteral preparation.
Centrally acting a2 agonists, clonidine, and dexmedetomidine have been used successfully as sedative agents, as well as for analgesia and management of withdrawal symptoms. Dexmedetomidine exhibits similar pharmacokinetics in children aged 4 months or older to that seen in adults. The major adverse effects of a2 agonists include hypotension and bradycardia, which can be of concern in the postcardiac surgery pediatric population. Abrupt discontinuation can cause rebound hypertension and thus tapering and gradual withdrawal is warranted  .
Other sedative agents that can be used in the PICU include propofol. It provides a sedative amnesic effect but with no analgesia. It is characterized by rapid onset and quick recovery with no active metabolites. It decreases sympathetic tone and thus may not be a suitable alternative in hemodynamically unstable patients. Other serious adverse effects include metabolic acidosis and hyperlipidemia. Propofol-related infusion syndrome (PRIS) has been reported and includes severe metabolic acidosis, hyperkalemia, lipemia, rhabdomyolysis, hepatomegaly, and cardiac and renal failure. Risk factors for developing PRIS include infusion greater than 4 mg/kg/h and duration of CI longer than 48 h. Therefore, its use should be limited to procedural sedation in the PICU [Table 5] , .
Ketamine can also be used as a sedative, analgesic, and opioid-sparing agent in the PICU. It acts at the cortex and limbic system to produce a dissociative state. Unlike other sedative agents such as benzodiazepines or opioids, it does not produce respiratory depression or hypotension and thus can be useful for procedural sedation and hemodynamically unstable patients. Several unique adverse effects linked to ketamine include hypertension, tachycardia, increased oral secretions, and increased intracranial pressure. Emergence phenomena upon recovery include hallucinations and delirium. These phenomena can be minimized by the coadministration of benzodiazepines.
| Approach to drug selection|| |
Several agents are available for pain and anxiety management in the PICU. Nonopioid or opioid analgesic agents should be administered at the beginning according to institutional pain scoring system to alleviate pain before the addition of sedative agents. Establishing a CI of analgesics and opioids appears to be more practical compared with intermittent intravenous boluses. Breakthrough pain can be managed either by administering intermittent intravenous bolus together with infusion or by increasing the baseline infusion rate.
Sedative and analgesic agents may be associated with numerous complications. Pain and sedation score should be used routinely to provide objective assessment and minimize these complications. A comprehensive scale such as the COMFORT-Behavioral scale is validated to assess both pain and sedation.
Careful tailoring of doses or agents used should be adopted according to the patients' hemodynamic state, respiratory state, and desired level of sedation. Nonopioids should be considered in mild-to-moderate pain, or as an adjuvant agent in moderate-to-severe pain to reduce opioid requirements. Fentanyl is the preferred agent as opposed to morphine as it has fewer hemodynamic effects, but opioid tolerance remains problematic. Thus, the addition of a sedative may be necessary to keep the child comfortable and avoid excessive opioid exposure. Children with hemodynamic instability or at risk for respiratory depression may benefit from the use of ketamine or dexmedetomidine. Propofol use should be limited to procedural sedation to avoid the risk of developing PRIS.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Pediatr Anesth 2011; 21:567-76.
Mendelsohn AB, Belle SH, Fischhoff B, Wisniewski SR, Degenholtz H, Chelluri L,QOL-MV Study Investigators. How patients feel about prolonged mechanical ventilation 1 year later. Crit Care Med 2002; 30:1439-45.
Pediatr Crit Care Med 2015; 16:e113-e118.
Wolf AR, Jackman L. Peidatr Anesth 2011; 21:567-576.
Ista E, van Dijk M, Tibboel D, de Hoog M. Assessment of sedation levels in pediatric intensive care patients can be improved by using the COMFORT ′behavior′ scale. Pediatr Crit Care Med 2005; 6:58-63.
Ramsay MA, Savege TM, Simpson BR, Goodwin R. Controlled sedation with alphaxalone-alphadotone. Br Med J 1974; 2:656-659.
Deeter KH, King MA, Ridling D, Irby GL, Lynn AM, Zimmerman JJ. Successful implementation of a pediatric sedation protocol for mechanically ventilated patients. Crit Care Med 2011; 39:683-688.
Merkel S, Voepel-Lewis T, Shayevitz JR, Malviya S. The FLACC scale: a behavioral scale for scoring postoperative pain in young children. Pediatr Nurs 1997; 23:293-297.
Franck LS, Harris SK, Soetenga DJ, Amling JK, Curley MA. The Withdrawal Assessment Tool-1 (WAT-1): an assessment instrument for monitoring opioid and benzodiazepine withdrawal symptoms in pediatric patients. Pediatr Crit Care Med 2008; 9:573-580.
Berde CB, Sethna NF. Drug therapy: analgesics for the treatment of pain in children. N Engl J Med 2002; 347:1094-1103.
Schechter NL, Allen A, Hanson K. Status of pediatric pain control: a comparison of hospital analgesic usage in children and adults. Pediatrics 1986; 77:11-15.
Lexi-Comp Inc. Lexi-Comp online, pediatric Lexi-drugs online
. Hudson, OH: Lexi-Comp Inc.; 2012.
Plate J, Goldstein LB Post-operative patient-controlled analgesia in pediatric patients. Available at: http://www.practicalpainmanagement.com/pain/acute/post-surgical/post-operative-patient-controlled-analgesia-pediatric-patients
. [Accessed 30 May 2012]
Zelter LK, Krane EJ. Pediatric pain management. Nelson′s textbook of pediatrics
. Saunders Publications; 2011:360-375.
Tobias JD. Tolerance, withdrawal, and physical dependency after long-term sedation and analgesia of children in the pediatric intensive care unit. Crit Care Med 2000; 28:2122-2132.
Darnell C, Steiner J, Szmuk P, Sheeran P. Withdrawal from multiple sedative agent therapy in an infant: is dexmedetomidine the cause or the cure? Pediatr Crit Care Med 2010; 11:e1-e3.
Timpe EM, Eichner SF, Phelps SJ. Propofol-related infusion syndrome in critically ill pediatric patients: coincidence, association, or causation? J Pediatr Pharmacol Ther 2006; 11:17-42.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]