Preoperative Evaluation, Premedication, and Induction of Anesthesia

Primary Smoking

Unfortunately, cigarette smoking is not only limited to adults. Each day, 3800 American adolescents smoke their first cigarette and of these, more than 50% will become regular smokers. The annual burden of smoking-attributable mortality remains high with 5.6 million youth currently 0 to 17 years of age projected to die prematurely from a smoking-related illness. Even though the rate of new cigarette smokers in North America has declined over the past 2 decades, this has been offset with an increase in use of other nicotine products such as electronic cigarettes (e-cigarettes). Many factors, including lack of regulation at the federal level, “harmless water vapor” messaging, a strong social media presence with celebrity endorsements, and flavors targeting a young audience (“Cupcake,” “Alien Blood,” “Cherry Crush,” “Chocolate Treat,” etc.) play a significant role in influencing initiation of e-cigarette use in this age group. A national survey indicated that e-cigarette use was at an all-time high among high school students at 13.4%, which was more prevalent than conventional cigarette use at 9.2%. Youth e-cigarette users are more likely than nonusers to report initiation of conventional cigarettes within a year.

Smoking is known to increase blood carboxyhemoglobin concentrations, decrease ciliary function, decrease functional vital capacity (FVC) and the forced expiratory flow in midphase (FEF _25%-75% ), and increase sputum production. There is extensive evidence that smokers undergoing surgery are more likely to develop wound infections and postoperative respiratory complications. Although stopping smoking for 2 days decreases carboxyhemoglobin levels and shifts the oxyhemoglobin dissociation curve to the right, stopping for at least 6 to 8 weeks is necessary to reduce the rate of postoperative pulmonary complications.

Current harmful effects of e-cigarette use focus on nicotine exposure, the potential for these products to be a gateway to cigarette use, and the possibility of exposure to harmful flavoring chemicals such as diacetyl (2,3-butanedione). This chemical is used to give foods a buttery or creamy flavor and has been shown to cause acute-onset bronchiolitis obliterans. Data are lacking on long-term exposure and health effects of the use of e-cigarettes given the limited time span these products have been in the marketplace.

The perioperative period is the ideal time to abandon the smoking habit permanently, and anesthesiologists can perhaps play a more active role in facilitating this process. Physician communication with adolescents regarding smoking cessation has been shown to positively impact their attitudes, knowledge, intentions to smoke, and quitting behaviors. In summary, during the preoperative visit with adolescents, anesthesiologists should inquire about cigarette smoking and emphasize the need to stop the habit by offering measures to ameliorate the withdrawal (e.g., nicotine patch).

Secondary Smoking

A national survey in the United States revealed the percentage of children 3 to 19 years of age without asthma exposed to environmental tobacco smoke (ETS) decreased from 57.3% to 44.2% from 1999 to 2010 while a higher percentage of children with asthma (54.0%) were exposed to ETS.

Studies have shown that children exposed to ETS are more likely to have asthma, otitis media, atopic eczema, hay fever, and dental caries. There is also an increased rate of lower respiratory tract illness in infants with ETS exposure. A recent systemic review and meta-analysis revealed a nearly 2-fold increase in risk of hospitalization for an asthma exacerbation in children with asthma and ETS in westernized countries. This is the first time this risk has been quantified and will enable health care providers to convey the harmful effects of ETS to parents about aggravation of asthma.

Several authors have demonstrated that ETS results in increased perioperative airway complications in children. In one study, urinary cotinine, the major metabolite of nicotine, was used as a surrogate marker of ETS. A strong association was found between passive inhalation of tobacco smoke and airway complications on induction and emergence from anesthesia. A prospective investigation in Australia provided further insight on the effect of the smoking habits of different family members; the risk for perioperative adverse respiratory events was higher when children were exposed to maternal or both parents smoking than when only the father smoked. Respiratory adverse events include laryngospasm, bronchospasm, airway obstruction, oxygen desaturation (<95%), severe or sustained cough, and stridor in the postanesthesia care unit (PACU).

The evidence for adverse perioperative events in children from ETS is clearly overwhelming. During the preoperative visit, the anesthesiologist should ascertain the child's exposure to ETS by asking parents or guardians about smoking within the household. This is an opportune time to educate parents and guardians about the dangers of ETS for their children.

Child Development and Behavior

Understanding age-appropriate behavior in response to external situations is essential. Age-specific perioperative anxieties are outlined in E-Table 4.2 (see also Chapter 3 for further discussion of risk factors for preoperative anxiety). Special aspects of a child's perception of anesthesia should be anticipated; children often have the same fears as adults but are unable to articulate them. The reason and need for a surgical procedure should also be carefully explained to the child. It is important to reassure children that anesthesia is not the same as the usual nightly sleep, but rather a special sleep caused by the medicines we give during which they cannot be awakened and no matter what the surgeon does, they cannot feel pain. Many children fear the possibility that they will wake up in the middle of the anesthetic and during surgery. They should be reassured that they will awaken only after the surgery is completed.

The words the anesthesiologist uses to describe to the child what can be anticipated must be carefully chosen, because children think concretely and tend to interpret the facts literally. Examples of this are presented by the following anecdotes:

• Example 1: A 4-year-old child was informed that in the morning she would receive a “shot” that would “put her to sleep.” That night, a frantic call was received from the mother, describing a very upset child; the child thought she was going to be “put to sleep” like the veterinarian had permanently “put to sleep” her sick pet.

• Example 2: A 5-year-old child admitted for elective inguinal herniorrhaphy received a heavy premedication and was deeply sedated on arrival in the OR. After discharge, the parents frequently discovered him wandering about the house at night. On questioning, the child stated that he was “protecting” his family. He stated: “I don't want anyone sneaking up on you and operating while you are sleeping.”

In the first example, the child's concrete thought processes misunderstood the anesthesiologist's choice of words. The second case represents a problem of communication: the child was never told he would have an operation.

The importance of proper psychological preparation for surgery should not be underestimated. Often, little has been explained to both patient and parents before the day of surgery. Anesthesiologists have a key role in defusing fear of the unknown if they understand a child's age-related perception of anesthesia and surgery (see Chapter 3 ). They can convey their understanding by presenting a calm and friendly face (smiling, looking at the child, and making eye contact), offering a warm introduction, touching the patient in a reassuring manner (holding a child's or parent's hand), and being completely honest. Children respond positively to an honest description of exactly what they can anticipate. This includes informing them of the slight discomfort of starting an IV line or giving an intramuscular premedication, the possible bitter taste of an oral premedication, or breathing our magic laughing gas through the flavored mask.

The postoperative process, from the OR to the recovery room, and the onset of postoperative pain should be described. Encourage the child and family to ask questions. Strategies to maintain analgesia should be discussed, including the use of long-acting local anesthetics; nerve blocks; neuraxial blocks; patient-controlled, nurse-controlled, or parent-controlled analgesia or epidural analgesia; or intermittent opioids (see also Chapter 42, Chapter 43, Chapter 44 ).

As children age, they become more aware of their bodies and may develop a fear of mutilation. Adolescents frequently appear quite independent and self-confident, but as a group, they have unique problems. In a moment their mood can change from an intelligent, mature adult to a very immature child who needs support and reassurance. Coping with a disability or illness is often very difficult for adolescents. Because they are often comparing their physical appearance with that of their peers, they may become especially anxious when they have a physical problem. In general, they want to know exactly what will transpire during the course of anesthesia. Adolescents are usually cooperative, preferring to be in control and unpremedicated preoperatively. The occasional overly anxious or rambunctious adolescent, however, may benefit from preanesthetic medication.

Monitoring the attitude and behavior of a child is very useful. A child who clings to the parents, avoids eye contact, and does not speak is very anxious. A self-assured, cocky child who “knows it all” may also be apprehensive or frightened. This know-it-all behavior may mask the child's true emotions, and he or she may decompensate just when cooperation is most needed. In some cases, nonpharmacologic supportive measures may be effective. In the extremely anxious child, supportive measures alone may be insufficient to reduce anxiety, and premedication is indicated.

Identifying a difficult parent or child preoperatively is not always easy, especially if the anesthesiologist first meets the child or family on the day of surgery and has limited time to assess the situation. Occasionally, we receive a warning regarding a difficult parent or child from the surgeon or nursing staff, based on their encounters with the family. With experience, some anesthesiologists are able to identify difficult parents and children during the short preoperative assessment and make appropriate adjustments to the anesthetic management plan.

The “veterans” or “frequent flyers” of anesthesia can also be difficult in the perioperative period. They have played the anesthesia and surgical game before and are not interested in participating again, especially if their previous experiences were negative. These children may benefit the most from a relatively heavy premedication; reviewing previous responses to premedication will aid in the adjustment of the current planned premedication (e.g., adding ketamine and atropine to oral midazolam to achieve a greater depth of sedation).

It is important to observe the family dynamics to better understand the child and determine who is in control, the parent or the child. Families many times are in a state of stress, particularly if the child has a chronic illness; these parents are often angry, guilt ridden, or simply exhausted. Ultimately, the manner in which a family copes with an illness largely determines how the child will cope. The well-organized, open, and communicative family tends to be supportive and resourceful, whereas the disorganized, noncommunicative, and dysfunctional family tends to be angry and frustrated. Dealing with a family and child from the latter category can be challenging. There is the occasional parent who is overbearing and demands total control of the situation. It is important to be empathetic and understanding but to set limits and clearly define the parent's role. He or she must be told that the anesthesiologist determines when the parent must leave the OR; this is particularly true if an unexpected development occurs during the induction.

Parental Presence During Induction

One controversial area in pediatric anesthesia is parental presence during induction. Some anesthesiologists encourage parents to be present at induction, whereas others are uncomfortable with the process and do not allow parents to be present. Inviting a parent to accompany the child to the OR has been interpreted by some courts as an implicit contract on the part of the caregiver who invited the parent to participate in the child's care; in one case, the institution was found to have assumed responsibility for a mother who suffered an injury when she fainted. Each child and family must be evaluated individually; what is good for one child and family may not be good for the next. (See Chapter 3 for a full discussion of this and other anxiolytic strategies in children.)

If the practice of having parents present at induction is to work well, then the anesthesiologist must be comfortable with such an arrangement. No parent should ever be forced to be present for the induction of anesthesia, nor should any anesthesiologist be forced into a situation that compromises the quality of care he or she affords a child in need.

Parents must be informed about what to anticipate in terms of the OR itself (e.g., equipment, surgical devices), in terms of what they may observe during induction (e.g., eyes rolling back, laryngeal noises, anesthetic monitor alarms, excitation), and when they will be asked to leave. They must also be instructed regarding their ability to assist during the induction process, such as by comforting the child, encouraging the child to trust the anesthesiologist, distracting the child, and consoling the child ( Videos 4.1 and 4.2 ). Personnel should be immediately available to escort parents back to the waiting area at the appropriate time. Someone should also be available to care for a parent who wishes to leave the induction area or who becomes lightheaded or faints. An anesthesiologist's anxiety about parents' presence during induction decreases significantly with experience.

Explaining what parents might see or hear is essential. We generally tell parents the following:

As you see your child fall asleep today, there are several things you might observe that you are not used to seeing. First, when anyone falls asleep, the eyes roll up, but since we are sleeping we do not generally see it. You may see your child do that today, and I do not want you to be frightened by that—it is expected and normal. The second thing is that as children go to sleep from the anesthesia medications, the tone of the structures in the neck decreases, so that some children will begin to snore or make vibrating noises. Again, I do not want you to be frightened or think that something is wrong. We expect this, and it is normal. The third thing you might see is what we call “excitement.” As the brain begins to go to sleep, it can actually get excited first. About 30 to 60 seconds after breathing the anesthesia medications, your child might suddenly look around or suddenly move his or her arms and legs. To you it appears that he or she is awakening from anesthesia or that he or she is upset. In reality, this is a good sign, because it indicates to us that your child is falling asleep and that 15 to 30 seconds later he or she will be completely anesthetized. Also, you should know that even though your child appears to be awake to you, in reality he or she will not remember any of that. As soon as your child loses consciousness, we will ask you to give your child a kiss and step out of the operating room.

This kind of careful preparation provides to the parents the confidence that the anesthesiologist really knows what he or she is talking about, and it avoids frightening the parents. In general, the more information provided, the lower the parental anxiety levels. A child-life specialist in surgical services may also prove valuable to the anesthesiologist by calming and preparing both children and parents for the OR experience (see “ Inhalation Induction ” later in this chapter for further details).

Occasionally, the best efforts to relieve a child's anxiety by parental presence or administration of a sedative premedication (or both) are not successful, and an anticipated smooth induction may not go as planned. There are three options that may be used depending on the age of the child: (1) renegotiating (which is seldom successful), (2) holding the mask farther away from the child's face, or (3) suggesting an IV or intramuscular induction. If an intramuscular shot or IV induction is proposed, the child will usually choose the mask. If the situation is totally out of control, either elective surgery can be rescheduled or intramuscular ketamine can be used if the parents choose to proceed. These situations are particularly difficult for the parents and the caregivers but must be handled on an individual basis.

Herbal Remedies

The use of herbal medicinal products has become increasingly popular, likely driven by the notion that “natural” substances have fewer side effects. A survey in five geographically diverse centers in the United States found that 3.5% of pediatric surgical patients had been given herbal supplements or homeopathic remedies 2 weeks prior to surgery. The findings of the National Health Interview Survey confirm a similar prevalence rate in which natural product usage among children age 0 to 17 years amounts to 3.9%. Herbal medicine use is more common in adults; 32% of adult surgical patients take one or more herb-related compounds. Nearly 70% of adults failed to disclose their use of herbal remedies when asked about medications during routine perioperative assessment. Herbal medicines are regulated as food supplements under the Dietary Supplement Health and Education Act of 1994 and as such manufacturers are not required to demonstrate safety or efficacy before placing a product on the market. Without the Food and Drug Administration (FDA) regulation, there are no quality assurance requirements for manufacturing and labeling and much variation can occur in each preparation. Anesthesiologists should include specific inquiries regarding the use of these medications because of the potential for adverse effects and drug interactions.

Herbal medicines are associated with cardiovascular instability, coagulation disturbances, potentiation of sedation, and immunosuppression. The most commonly used herbal medications reported are garlic, ginseng, Ginkgo biloba , St. John's wort, and Echinacea, with Echinacea and other herbal medicines for the treatment of coughs and colds taking the lead in the pediatric population. The three “g” herbals, together with feverfew (Tanacetum parthenium), potentially increase the risk of bleeding during surgery. The amount of active ingredient in each preparation and the dose taken may vary, thus making detection of a change in platelet function and other subtle coagulation disturbances difficult. St. John's wort is the herb that most commonly interacts with anesthetics and other medications, usually via a change in drug metabolism, because of potent inducing effects on the cytochrome P-450 enzymes (e.g., CYP3A4) and P-glycoprotein. A potentially fatal interaction between cyclosporine and St. John's wort has been well documented. Heart, kidney, or liver transplant recipients who were stabilized on a dose of cyclosporine experienced decreased plasma concentrations of cyclosporine and, in some cases, acute rejection episodes after taking St. John's wort. A summary of the most commonly used herbal remedies and their potential perioperative complications is shown in E-Table 4.4 .

To avoid potential perioperative complications, the ASA has encouraged the discontinuation of all herbal medicines 2 weeks before surgery, although this recommendation is not evidence based. Recognizing that this is not always feasible, the ASA further recommends that anesthesiologists have knowledge of herbal medications and their potential interactions. Each herb should be carefully evaluated using standard resource texts, and a decision should be made regarding the timing of or need for discontinuation as determined on a case-by-case basis.

Anesthesia and Vaccination

Children may present for surgery after having been recently immunized. The anesthesiologist and surgeon must then consider (1) whether the immunomodulatory effects of anesthesia and surgery might affect the efficacy and safety of the vaccine and (2) whether the inflammatory responses to the vaccine will alter the perioperative course.

What do anesthesiologists think about anesthesia and vaccination? An international survey revealed that only one-third of responding anesthesiologists had the benefit of a hospital policy, ranging from a formal decision to delay surgery to an independent choice by the anesthesiologist. Sixty percent of respondents would anesthetize a child for elective surgery within 1 week of receiving a live attenuated vaccine (such as oral polio vaccine or measles, mumps, and rubella [MMR] vaccine), whereas 40% would not. The survey also revealed that 28% of anesthesiologists would delay immunization for 2 to 30 days after surgery.

A scientific review of the literature associating anesthesia and vaccination in children resulted in recommendations for the care of children under these circumstances. The review demonstrated a brief and reversible influence of vaccination on lymphoproliferative responses that generally returned to preoperative values within 2 days. Vaccine-driven adverse events (e.g., fever, pain, irritability) might occur but should not be confused with perioperative complications. Adverse events to inactivated vaccines such as diphtheria-tetanus-pertussis (DPT) become apparent from 2 days and to live attenuated vaccines such as MMR from 7 to 21 days after immunization. Therefore appropriate delays between immunization and anesthesia are recommended by type of vaccine to avoid misinterpretation of vaccine-associated adverse events as perioperative complications. Because children remain at risk of contracting vaccine-preventable diseases, the minimum delay seems prudent, especially in the first year of life. Likewise, it seems reasonable to delay vaccination after surgery until the child is fully recovered. These recommendations were adopted in a consensus guideline by the Association of Paediatric Anaesthetists of Great Britain and Ireland, ^*

* See http://www.apagbi.org.uk/sites/default/files/images/Final%20Immunisation%20apa.pdf (accessed March 27, 2016).

though to date, the US Centers for Disease Control and Prevention does not have a policy regarding the timing of vaccinations and surgery. Other immunocompromised patients, such as human immunodeficiency virus (HIV)-positive children, cancer patients, and transplant recipients, have distinct underlying immune impairments, and the influence of anesthesia on vaccine responses has not been comprehensively investigated.

Allergies to Medications and Latex

The details pertaining to all allergies to medications and materials should be described in the child's record. These include the age of onset, frequency, severity, investigations, and treatments. The vast majority of reported allergies on children's charts are either nonimmunologic reactions or known (or unknown) drug adverse effects. The most common medication- and hospital-related allergies in children are penicillin and latex allergy.

Most cases of reported penicillin allergy consist of a maculopapular rash after oral penicillin. This occurs in 1% to 4% of children receiving penicillin or in 3% to 7% of those taking ampicillin, usually during treatment. Rarely are signs or symptoms that suggest an acute (immunoglobulin E–mediated) allergic reaction present (i.e., angioedema), and even less frequently is skin testing conducted to establish penicillin allergy. Given the frequency of penicillin allergy, most of these unverified allergies in fact are not allergies to penicillin but rather minor allergies to the dye in the liquid vehicle or a consequence of the (viral) infection. If the child has not received penicillin for at least 5 years since the initial exposure and has not been diagnosed with a penicillin allergy by an immunologist or allergist, then a reexposure is warranted. If the child has been tested immunologically for penicillin allergy, then it is best to avoid this class of antibiotics. Although there is a 5% to 10% cross-reactivity between first-generation cephalosporins and penicillin, there is no similar cross-reactivity with second- and third-generation cephalosporins. To date, there have been no fatal anaphylactic reactions in penicillin-allergic children from a cephalosporin.

Latex allergy is an acquired immunologic sensitivity resulting from repeated exposure to latex, usually on mucous membranes (e.g., children with spina bifida or congenital urologic abnormalities who have undergone repeated bladder catheterizations with latex catheters, those with more than four surgeries, those requiring home ventilation). It occurs more frequently in atopic individuals and in those with certain fruit and vegetable allergies (e.g., banana, chestnut, avocado, kiwi, pineapple). For a diagnosis of latex anaphylaxis, the child should have personally experienced an anaphylactic reaction to latex, skin-tested positive for anaphylaxis to latex, or experienced swelling of the lips after touching a toy balloon to the lips or a swollen tongue after a dentist inserted a rubber dam into the mouth. The avoidance of latex within the hospital will prevent acute anaphylactic reactions to latex in children who are at risk. Latex gloves and other latex-containing products should be removed from the immediate vicinity of the child. Prophylactic therapy with histamine H ₁ - and H ₂ -receptor antagonists and steroids do not prevent latex anaphylaxis. Latex anaphylaxis should be treated by removal of the source of latex, administration of 100% oxygen, acute volume loading with balanced salt solution (10 to 20 mL/kg repeated until the systolic blood pressure stabilizes), and administration of IV epinephrine (1 to 10 µg/kg according to the severity of the anaphylaxis). In some severe reactions, a continuous infusion of epinephrine alone (0.01 to 0.2 µg/kg per minute) or combined with other vasoactive medications may be required for several hours.

Family History

It is important to inquire about a family history, particularly focusing on a number of conditions, including malignant hyperthermia, muscular dystrophy, prolonged paralysis associated with anesthesia (pseudocholinesterase deficiency), sickle cell disease, bleeding (and bruising) tendencies, and drug addiction (drug withdrawal, HIV infection). The precise relationship to the proband must be documented.

Tranquilizers

The major effect of tranquilizers is to allay anxiety, but they also have the potential to produce sedation. This group of drugs includes the benzodiazepines, phenothiazines, and butyrophenones. Benzodiazepines are widely used in children, whereas phenothiazines and butyrophenones are infrequently used.

Benzodiazepines

Benzodiazepines calm children, allay anxiety, and diminish recall of perianesthetic events. At low doses, minimal drowsiness and cardiovascular or respiratory depression are produced.

Midazolam, a short-acting, water-soluble benzodiazepine with an elimination half-life of approximately 2 hours, is the most widely used premedication for children. The major advantage of midazolam over other drugs in its class is its rapid uptake and elimination. It can be administered intravenously, intramuscularly, nasally, orally, and rectally with minimal irritation, although it leaves a bitter taste in the mouth or nasopharynx after oral or nasal administration. Most children are adequately sedated after receiving a midazolam dose of 0.025 to 0.1 mg/kg intravenously, 0.1 to 0.2 mg/kg intramuscularly, 0.25 to 0.75 mg/kg orally, 0.2 mg/kg nasally, or 1 mg/kg rectally.

Orally administered midazolam is effective in calming most children and does not increase gastric pH or residual volume. Evidence suggests that the required dose of midazolam increases as age decreases in children, similar to that for inhaled agents and IV agents. An increased clearance in younger children contributes to their increased dose requirement. A number of medications that affect the cytochrome oxidase system significantly affect the first-pass metabolism of midazolam, including grapefruit juice, erythromycin, protease inhibitors, and calcium-channel blockers that decrease CYP3A4 activity, which in turn increases the blood concentration of midazolam and prolongs sedation. Conversely, anticonvulsants (phenytoin and carbamazepine), rifampin, St. John's wort, glucocorticoids, and barbiturates induce the CYP3A4 isoenzyme, thereby reducing the blood concentration of midazolam and its duration of action. The dose of oral midazolam should be adjusted in children who are taking these medications.

Concerns have been raised about possible delayed discharge after premedication with oral midazolam. Oral midazolam, 0.5 mg/kg, administered to children 1 to 10 years of age, did not affect awakening times, time to extubation, postanesthesia care unit, or hospital discharge times, after sevoflurane anesthesia. Similar results have been reported in children and adolescents after 20 mg of oral midazolam; however, detectable preoperative sedation in this group of children was predictive of delayed emergence. In children aged 1 to 3 years undergoing adenoidectomy as outpatients, premedication with oral midazolam, 0.5 mg/kg, slightly delayed spontaneous eye opening by 4 minutes and discharge by 10 minutes compared with placebo; children who had been premedicated, however, exhibited a more peaceful sleep at home on the night after surgery.

Likely the greatest effect of oral midazolam on recovery occurs with its use in children undergoing myringotomy and tube insertion, a procedure that normally takes 5 to 7 minutes. After oral midazolam premedication (0.5 mg/kg), induction of anesthesia with propofol, and maintenance with sevoflurane, emergence and early recovery were delayed by 6 and 14 minutes, respectively, in children 1 to 3 years of age compared with unpremedicated children, although discharge times did not differ. Increased postoperative sedation may be attributed to synergism between propofol and midazolam on γ-aminobutyric acid (GABA) receptors.

Although anxiolysis and a mild degree of sedation occur in most children after midazolam, a few develop undesirable adverse effects. Some children become agitated after oral midazolam. If this occurs after IV midazolam (0.1 mg/kg), IV ketamine (0.5 mg/kg) may reverse the agitation.

Anxiolysis and sedation usually occur within 10 minutes after intranasal midazolam ; nasal administration is not well accepted because it produces irritation, discomfort, and a burning aftertaste. Another theoretical concern for the nasal route of administration of midazolam is its potential to cause neurotoxicity via the cribriform plate. There are direct connections between the nasal mucosa and the central nervous system (CNS) ( E-Fig. 4.2 ). Medications administered nasally reach high concentrations in the cerebrospinal fluid very quickly. To date, no such sequelae have been reported. Because midazolam with preservative has been shown to cause neurotoxicity in animals, we recommend only preservative-free midazolam for nasal administration.

Sublingual midazolam (0.2 mg/kg) has been reported to be as effective as, and better accepted than, intranasal midazolam. Oral transmucosal midazolam given in three to five small allotments (0.2 mg/kg total dose) placed on a child's tongue (8 months to 6 years of age) was found to provide satisfactory acceptance and separation from parents in 95% of children.

Diazepam is used only for premedication of older children. In infants and especially preterm neonates, the elimination half-life of diazepam is markedly prolonged because of immature hepatic function (see Chapter 7 ). In addition, the active metabolite (desmethyldiazepam) has pharmacologic activity equal to that of the parent compound and a half-life of up to 9 days in adults. The most effective route of administration of diazepam is intravenous, followed by oral and rectal. The intramuscular route is not recommended because it is painful and absorption is erratic. The average oral dose for premedicating healthy children with diazepam ranges from 0.1 to 0.3 mg/kg; however, doses as large as 0.5 mg/kg have been used. The recommended dose of rectal diazepam is 1 mg/kg, and the peak serum concentration is reached after approximately 20 minutes. Compared with rectal midazolam, rectal diazepam is less effective.

Lorazepam (0.05 mg/kg) is reserved primarily for older children. Lorazepam causes less tissue irritation and more reliable amnesia than diazepam. It can be administered orally, intravenously, or intramuscularly and is metabolized in the liver to inactive metabolites. Compared with diazepam, the onset of action of lorazepam is slower and its duration of action is prolonged. The IV formulation of lorazepam is avoided in neonates because it may be neurotoxic.

Barbiturates

Barbiturates are infrequently used for premedication as they have been replaced by oral midazolam. The advantages of barbiturates include minimal respiratory or cardiovascular depression, anticonvulsant effects, and a very low incidence of nausea and vomiting.

The relatively short-acting barbiturates thiopental and methohexital may be given rectally as a 10% solution in the presence of the parents who may hold the toddler until he or she is sedated. The usual dose of rectal thiopental or methohexital is 30 mg/kg via a shortened suction catheter, which produces sleep in about two-thirds of the children within 15 minutes. In some cases, the sedation may be profound, resulting in airway obstruction and laryngospasm. Hence, all children should be closely monitored with a source of oxygen, suction, and a means for providing ventilatory support; rectally administered methohexital has been reported to cause apnea in children with meningomyelocele. Children chronically treated with phenobarbital or phenytoin are more resistant to the effects of rectally administered methohexital, probably because of enzyme induction.

Additional disadvantages of rectal methohexital include unpredictable systemic absorption, defecation after administration, and hiccups. Contraindications to methohexital include hypersensitivity, temporal lobe epilepsy, and latent or overt porphyria. Rectal methohexital is also contraindicated in children with rectal mucosal tears or hemorrhoids because large quantities of the drug can be absorbed, resulting in respiratory or cardiac arrest.