1535 128 Anesthesia Effects on Organ Systems LINDSAY M STOLLINGS, PETER J DAVIS, ALISON M ELLIS, AND ANTONIO CASSARA • The anesthetic care of ICU patients is an extension of medical and anesthetic man[.]
128 Anesthesia Effects on Organ Systems LINDSAY M STOLLINGS, PETER J DAVIS, ALISON M ELLIS, AND ANTONIO CASSARA PEARLS • • The anesthetic care of ICU patients is an extension of medical and anesthetic management principles employed in the operating room Anesthesiologists caring for critically ill children must understand the desired therapeutic goals and each patient’s preexisting conditions Anesthetic Agents and Regional Anesthesia Methods Anesthetic agents alter normal homeostasis in patients with critical disease and/or trauma These physiologic effects and consequences can be profound Anesthetic agents have been shown to both be protective and detrimental to organ systems An understanding of these effects is imperative to providing quality care for all patients, especially intensive care unit (ICU) patients.1–3 This chapter focuses on the most commonly used volatile and intravenous hypnotic and opioid medications The use of local anesthetic agents and their clinical applications for pediatric ICU patients is also addressed Volatile or inhaled anesthetics are a key component of a balanced anesthetic regimen The most frequently used inhaled agents are sevoflurane, isoflurane, and desflurane While these all induce a state of unconsciousness and amnesia, each has distinct characteristics that may influence the selection of a particular agent for a specific clinical indication Sevoflurane is the most commonly administered anesthetic for children It can promote a rapid and smooth induction of anesthesia, as opposed to desflurane, which is a strong airway irritant that can cause coughing, laryngospasm, and hypoxemia.4 When comparing the anesthetic effects of inhalational agents, the concept of minimal alveolar concentration (MAC) is used MAC is defined as the concentration that prevents movement in 50% of patients in response to a surgical incision The use of MAC as a metric allows one to compare anesthetics of different potencies at a similar effect (MAC multiples) rather than comparing similar concentrations of drugs with differing potencies In addition to inhaled agents, balanced anesthesia includes the use of intravenous anesthetics such as propofol and dexmedetomidine • • ICU physicians must be aware of the physiologic perturbations of anesthesia and surgery in pediatric patients to adapt management appropriately and understand the rationale for using particular agents Understanding both long- and short-term anesthetic effects on various organ systems is still a growing field of research Propofol is a sedative hypnotic that is widely used as an induction agent in anesthesia as well as in continuous infusion for sedation in the ICU It is rapidly distributed and cleared Propofol is suspended in a lipid emulsion and a continuous infusion can result in a significant lipid load Dexmedetomidine, a highly selective a2adrenergic agonist, is a sedative analgesic used for both procedural and pediatric ICU sedation It produces anxiolysis and analgesia via stimulation of a2-receptors in the brain and spinal cord and reduces the requirement for inhaled anesthetics and opioids.5,6 Dexmedetomidine has a rapid distribution phase and an elimination half-life of hours.7,8 The pharmacokinetic profile in 2- to 12-year-old children is similar to that of adults, whereas clearance in 1- to 24-month-old infants is faster than in adults.9 Because inhalational anesthetics can produce significant hemodynamic changes in compromised children, the use of high-dose opioids has been shown to confer hemodynamic stability and adequate anesthesia.10,11 Frequently used opioids include fentanyl, remifentanil, and sufentanil However, while high-dose opioid regimens promote hemodynamic stability, they delay neurologic recovery and cause respiratory depression.12–14 Opioids such as fentanyl and sufentanil, which undergo hepatic elimination, increase their terminal half-life with repeated doses Remifentanil, a synthetic opioid, is metabolized by plasma and tissue esterases; thus, it has a more reliable pharmacokinetic profile, an extremely short half-life, and is not influenced by the duration of infusion Fig 128.1 depicts timing of decrease in site effect after termination of opioid infusion as a function of the duration of the infusion Additionally, remifentanil clearance peaks in neonates and infants, and its terminal elimination half-life does not change with age.15 This is in direct contrast to other opioid agents—such as fentanyl, sufentanil, and morphine—which have the lowest clearance and longest elimination half-time during infancy Thus, 1535 1536 SECTION XIV Pediatric Critical Care: Anesthesia Principles in the Pediatric Intensive Care Unit Minutes required for a decrease in effects site concentration the pharmacokinetic and dynamic effects of remifentanil are more predictable than for the organ-eliminated opioids Unfortunately, tolerance and hyperalgesia have been reported with remifentanil administration, limiting its potential use Local anesthetics and regional anesthesia are frequently employed components of anesthetic regimens Local anesthetic use in regional anesthesia for children significantly improves perioperative pain and has the potential to decrease opioid consumption Unlike in adults, most regional anesthetics in the pediatric population are performed under general anesthesia and with ultrasound guidance This direct visualization of anatomy and local anesthetic infiltration has improved the quality of these nerve blocks Ultrasound use has also decreased the incidence of nerve injury and decreased the amount of local anesthetic necessary to provide adequate pain control.16-19 Local anesthetics are organized into two categories: amino esters and amino amides Esters include cocaine, tetracaine, chloroprocaine, and prilocaine and are associated with allergic responses These agents are metabolized by plasma and tissue esterases Amide agents—which include bupivacaine, ropivacaine, levobupivacaine, and lidocaine—are more commonly employed for both central and peripheral nerve blockade in the pediatric population due to a more favorable toxicity profile.20 These agents are metabolized by the P-450 system within the liver Duration of action is the shortest in neonates and infants Commonly performed blocks in the pediatric population include paravertebral, transversus abdominis plane (TAP), and the rectus sheath blocks More recently, other types of nerve blocks, including blocks of the quadratus lumborum (QL) and erector spinae planes, are being performed All of these regional anesthetics are considered peripheral nerve blocks and thus have fewer contraindications and complications than neuraxial blocks in critically ill patients The paravertebral nerve block can be performed in the setting of multiple rib fractures due to trauma or major thoracic or abdominal procedures Local anesthetic is injected into the paravertebral space, resulting in blockade of the somatic and sympathetic nerves that exit at the level of injection (Fig 128.2) Recently, anesthetists have been performing erector spinae plane blocks instead of paravertebral blocks owing to their ease of placement In this block, local anesthetic is injected under the erector spinae muscle, lifting it upward, resulting in a similar blockade (Fig 128.3) Additional peripheral nerve blocks indicated for abdominal procedures include the TAP block, rectus sheath, and QL block A TAP block involves local anesthetic injection between Fentanyl Alfentanil Sufentanil Remifentanil 120 90 50% decrease 60 30 120 240 360 480 Infusion duration (minutes) 600 • Fig 128.1 Fentanyl, alfentanil, and sufentanil recovery curves. Time required for 50% decrease in effects site concentration after termination of infusion (From Wolf A, Weir P, Segar P, Stone J, Shield J Impaired fatty acid oxidation in propofol infusion syndrome Lancet 2001;357[9256]: 606–607 ) Left lung Right lung Oes Sympathetic ganglion Az Rami communicantes Td Ao Visceral pleura Parietal pleura Bd Intercostal nerve Endothoracic fascia Inn IM Tp Int IM Ext IM Dorsal ramus of spinal nerve Sp Needle • Fig 128.2 Paravertebral nerve blockade and the paravertebral space. The needle is advanced into the paravertebral space Ao, Aorta; Az, azygous; Bd, vertebral body; Ext IM, external intercostal muscle; Inn IM, innermost intercostal muscle; Int IM, internal intercostal muscle; Oes, esophagus; Sp, spinous process; Td, thoracic duct; Tp, transverse process (From Cowie B, McGlade D, Ivanusic J, Barrington MJ Ultrasound-guided thoracic paravertebral blockade: a cadaveric study Anesth Analg 2010;110[6]:1735–1739 ) CHAPTER 128 Anesthesia Effects on Organ Systems Ne Ne ed ed le le ESM ESM Transverse process Transverse process A 1537 B Cranial Caudad Cranial Caudad • Fig 128.3 Erector spinae plane block. Ultrasound-guided image of needle at the transverse process and overlying erector spinae muscle (ESM, A) and distribution of local anesthetic spread (B) (From Eng HC, Chin KJ, Adhikary, SD How I it: erector spinae block for rib fractures The Penn State Health Experience ASRA News, 2018.) External oblique Internal oblique Transversus abdominis Peritoneal cavity Medial Lateral B A • Fig 128.4 Anatomy of the transverse abdominis plane block. (A) Typical nerve distribution (B) Ultrasound view of anterolateral abdominal wall and muscle layers the internal oblique and transverse abdominis muscles where the thoracolumbar nerves lie, which is effective for laparoscopic procedures (Fig 128.4) More specifically, a rectus sheath block, where local anesthetic is injected between the posterior aspect of the rectus muscle and the posterior rectus sheath (Fig 128.5), can be used for procedures involving the umbilicus Finally, a QL block is used for abdominal surgery below the umbilicus (Fig 128.6) At least three different needle approaches have been described, but no definitive evidence proves one more efficacious than another Local anesthetic is injected in the plane surrounding the QL; the more specific location is determined by various needle approaches When employing regional anesthesia as either a primary anesthetic or adjunct to an anesthetic regimen, local anesthetic systemic toxicity (LAST) must be considered LAST is a severe complication of local anesthetic use; children are at increased risk owing to lower concentrations of serum-binding proteins (a-1acid glycoprotein and albumin) A slower rate of metabolism can also predispose children to LAST This reaction is a combination of both neurologic and cardiovascular collapse, during which neurologic symptoms typically present first.21,22 In the anesthetized patient, these symptoms can include muscle rigidity, increased blood pressure and heart rate, and seizure, followed by cardiovascular collapse Prompt recognition and treatment with lipid emulsion is essential.23 An initial dose of 1.0 to 1.5 mL/kg (maximum, 10 mL/kg) 20% intralipid is followed by continuous infusion 0.25 to 0.5 mL/kg per minute in addition to any airway management or other supportive measures that are necessary Neurologic Effects The neurologic impact of anesthetic agents should be considered carefully in both healthy and critically ill patients throughout the perioperative setting Traumatic brain injury is a leading form of pediatric trauma in the United States.24,25 Measures to control intracranial hypertension, typically associated with poor outcomes, are employed throughout the perioperative period Specifically, maintaining cerebral perfusion pressure is imperative to 1538 S E C T I O N X I V Pediatric Critical Care: Anesthesia Principles in the Pediatric Intensive Care Unit RAM Rectus sheath (posterior aspect) A Lateral RAM Rectus sheath (posterior aspect) B • Fig 128.5 Rectus sheath nerve block. Needle path with needle head positioned between the posterior rectus abdominis muscle (RAM) and the rectus sheath (A) and spread of local anesthetic within the posterior rectus sheath (B) (From NYSORA Truncal and cutaneous blocks https://www.nysora.com/ techniques/truncal-and-cutaneous-blocks/truncal-and-cutaneous-blocks.) maintain neurologic function and is defined as the difference between mean arterial pressure (MAP) and intracranial pressure (ICP) or central venous pressure Intracranial hypertension is defined as ICP greater than or equal to 15 to 20 mm Hg and increased systemic blood pressure is necessary to maintain cerebral perfusion Signs of intracranial hypertension are listed in Table 128.1 In patients with supratentorial lesions, MAC of desflurane increased ICP, whereas an equal dose of isoflurane did not.26 This may be a result of increased cerebral spinal fluid production with the use of desflurane.27 The most dynamic of the intracranial compartments (cerebral tissue, blood, cerebral spinal fluid) is blood volume, mediated primarily through cerebral vascular resistance Factors that influence cerebral vascular resistance and cerebral blood flow (CBF) include arterial partial pressure of carbon dioxide (Paco2) and oxygen (Pao2), MAP, and various drugs, such as anesthetic agents (Fig 128.7) The brain maintains a constant CBF over a MAP ranging from 50 to 150 mm Hg in adults, known as cerebral autoregulation This range likely shifts in concert with age-related changes in normal system blood pressures and cerebral perfusion pressures in infants and children It may also shift in the setting of chronic hypertension, intracranial tumors, head trauma, or shock, thereby sensitizing the brain to ischemic effects.28,29 CBF varies linearly by 2% to 4% for every mm Hg of Paco2; anesthetized children exhibit greater vasoreactivity than adults.28 As Paco2 is lowered, cerebral vasoconstriction occurs, thus decreasing CBF As it approaches 20 mm Hg, vasoconstriction can be significant enough to result in ischemia This relationship is limited, and a diminished effect is seen over time Pao2 less than 50 mm Hg results in cerebral vasodilation and increased CBF, whereas hyperoxemia exceeding 300 mm Hg may result in vasoconstriction Generally, inhaled anesthetics impair autoregulation and increase CBF The effect of volatile anesthetics on autoregulation can be seen in Fig 128.8 Sevoflurane preserved autoregulation up to 1.5 MAC, whereas MAC of desflurane impaired cerebral autoregulation, and at 1.5 MAC it was abolished.30,31 Sevoflurane also better preserved autoregulation and had less of a vasodilatory effect than isoflurane.27,32 In contrast, propofol at 200 mg/kg minute had no effect on autoregulation.33 Furthermore, the effect of Paco2 on CBF was more pronounced during isoflurane anesthesia than with sevoflurane.34 CBF values were measured via labeled magnetic resonance imaging (MRI) and found to be approximately 2.5 to times lower in most regions during a fentanyl anesthetic versus isoflurane.35 However, opioid anesthetics in conjunction with propofol have been shown to maintain cerebral autoregulation.36 Cerebral metabolism—specifically, the cerebral metabolic rate of oxygen (CMRO2), is also affected by anesthetic agents Volatile agents “uncouple” the normal relationship between CBF and CMRO2, resulting in increased vasodilation However, isoflurane appears to decrease CBF with associated hyperventilation to a Paco2 to 20 to 25 mm Hg.37 In contrast, nitrous oxide is known to cause cerebral vasodilation and increase the CMRO2, effects that may be countered by the addition of intravenous agents Sevoflurane has been shown to increase CBF and ICP while decreasing the CMRO2.38 Desflurane and isoflurane have similar effects on CBF and exhibit burst suppression at 1.24 MAC.39 Propofol produces global metabolic depression and decreased CMRO2, CBF, and ICP while preserving the response to arterial CO2.28,40–43 Intravenous agents are also able to modify CBF and cerebral metabolism When measuring cerebral tissue oxygenation, MAP, heart rate, Pao2, Paco2, hemoglobin, and middle cerebral artery (MCA) mean flow velocity at various time points following a bolus administration of mg/kg of propofol, cerebral tissue oxygenation and MCA flow velocity were shown to decrease without significant decrease in the other end points.44 In a study comparing the effects of dexmedetomidine, sevoflurane, and propofol on cerebral metabolism in 150 healthy male subjects, dexmedetomidine and propofol decreased cerebral metabolism most significantly.45 This is an important finding when considering possible dexmedetomidine-induced cerebral vasoconstriction or cerebral hypoperfusion related to anesthesia or surgical procedure Further study comparing dexmedetomidine and propofol revealed that dexmedetomidine provided deeper sedation during deep brain stimulation while maintaining cerebral perfusion pressure, CBF CHAPTER 128 Anesthesia Effects on Organ Systems 1539 QLB1 External oblique muscle Internal oblique muscle QLB2 Transversus abdominalis muscle Latissimus dorsi muscle Quadratus lumborum muscle Transmuscular QLB Middle TLF Anterior TLF Spinal nerve Posterior TLF Psoas major muscle Lumbar artery Articular process Erector spinae muscle Vertebral body A lateral LD EQ p o s t e r i o r QL RP IO TA PM P ES TP VB A B • Fig 128.6 Quadratus lumborum block (QLB). (A) Three needle approaches to perform the QL1, QL2, and QL3 block (B) Ultrasound image of the lateral abdominal wall Arrows denote the lumbar plexus; arrowheads denote the transverse abdominis aponeurosis A, Aorta; EO, external oblique; ES, erector spinae; IO, internal oblique; LD, latissimus dorsi; P, peritoneal space; PM, psoas major; QL, quadratus lumborum; RP, retroperitoneal space; TA, transverse abdominis; TP, transverse process; VB, vertebral body (From NYSORA Ultrasound-guided transversus abdominis plane and quadratus lumborum blocks https://www.nysora.com/regional-anesthesiafor-specific-surgical-procedures/abdomen/ultrasound-guided-transversusabdominis-plane-quadratus-lumborum-blocks.) TABLE 128.1 Signs of Intracranial Hypertension in Infants and Children Infants Children Infants and Children Irritability Headache Decreased consciousness Full fontanelle Diplopia Cranial nerve (III and VI) palsies Widely separated cranial sutures Papilledema Loss of upward gaze (setting sun sign) Cranial enlargement Vomiting Signs of herniation, Cushing triad, pupillary changes ... in the pediatric population are performed under general anesthesia and with ultrasound guidance This direct visualization of anatomy and local anesthetic infiltration has improved the quality... due to a more favorable toxicity profile.20 These agents are metabolized by the P-450 system within the liver Duration of action is the shortest in neonates and infants Commonly performed blocks... erector spinae plane blocks instead of paravertebral blocks owing to their ease of placement In this block, local anesthetic is injected under the erector spinae muscle, lifting it upward, resulting