Fig. 3.1
Play preparation for anesthesia by Giocamico
Specialists also prepare children who have to undergo painful procedures in sedation analgesia.
Also promising is the preparation of children aged 5–10 years old for MRI. The aim is to reduce the number of MRI done under general anesthesia (Fig. 3.2).
Fig 3.2
Play preparation for MNR by Giocamico®
3.1.3 Parental Presence During Induction of Anesthesia (PPIA)
In 1985, an ophthalmic surgeon, Adrian While, wrote in the British Medical Journal that he had not been allowed to accompany his 3-year-old daughter to the operating room for induction and argued that parents should be admitted to the operating room to help their child. Gauderer indicated that virtually all parents, given a choice, went into the operating room with their children; only two parents had a fainting spell. Nurses, anesthesiologists, and surgeons were excited about this new approach, which appeared to be safe, simple, and effective [13]. A study by Kain compared PPIA to drug preparation and demonstrated that children who were premedicated had a lesser degree of anxiety at the time of separation before induction compared to the control group and to the PPIA group [14]. In another study, the presence of a parent in the room did not reduce the anxiety of the child who had already received midazolam, while there was a reduction in the anxiety of the parents and their greater satisfaction [15].
Nevertheless, it seems that children aged older than 4 and anxious parents might get some benefit from PPIA [9].
Lerman believes that the presence of the parents is not an undeniable right but rather a therapeutic option to facilitate the induction of anesthesia to be used at the sole discretion of the anesthesiologist [16]. Despite this theory, there is no doubt that some children (such as those with special needs, very anxious, or subjected to multiple hospitalizations) may actually benefit from PPIA, which should ideally be preceded by a preparation program for parents.
In our experience, of over 15 years, we propose that one of the parents accompanies the child into the operating room for induction of anesthesia, excluding pregnant moms, parents with health problems, and anxious parents to whom we explain that their presence could increase the child’s anxiety and create problems for the staff. When the parent comes into the room, the preschoolers are normally premedicated with midazolam, while older children can choose, in agreement with the parent, whether or not to have premedication. They can also choose the type of induction of anesthesia, inhalation or intravenous, which helped in the choice by the anesthesiologist. A staff member accompanies the parent in every moment of his stay in the operating room.
Different “side effects” of PPIA have been described in the literature: parents taking their children out of the operating room, parents who faint, and even parents who want the anesthesiologist to discontinue anesthesia and awaken their child. Hence, it is important to select the right parents (excluding, e.g., those who are anxious) and possibly make them undergo a preparation process. In addition, it is important to have a staff member always close to the parent. This member will escort the parent outside the operating room at the end of induction or whenever the child’s condition changes and the parents’ presence might be distracting or disruptive to the induction of anesthesia.
Hospitalization before surgery and prolonged preoperative fasting represent for the child an additional source of discomfort. At our hospital, young patients can be admitted 1–2 h before surgery. Regarding preoperative fasting, it is necessary to minimize the fasting hours (especially in smaller patients) in accordance with the directions of the American Society of Anesthesiology for healthy pediatric patients undergoing elective surgery (see below). In particular, the reduction in fasting hours is not associated with an increased gastric residual volume, or indirect index of risk of aspiration pneumonia. Furthermore, a less restrictive fasting regimen reduces dehydration, increases hemodynamic stability during anesthesia, facilitates venous vascular access, guarantees glucose homeostasis, reduces irritability in the young patient, and increases the overall satisfaction of the child and parents.
The pain from venipuncture is one of the greatest fears of the hospitalized pediatric patient. The pain generated by venipuncture is classified as moderate to severe. The procedure should be reduced to the absolute minimum, such as preoperative blood tests prescribed only on the basis of anomalies detected in the patient history or by physical examination [17]. The intravenous line needed for the surgery is normally placed after induction of anesthesia when the child is asleep and the veins well dilated. However, if the child prefers an intravenous induction, it is recommended to apply an anesthetic cream over the skin of the most visible veins 40 minutes before the surgery.
3.2 Pharmacological Preparation
The second part of this chapter will briefly review only the most widespread routes of administration of the most common drugs that are currently used for pharmacological preparation of children before surgery.
The goals of premedication in children are the reduction in anxiety, block of autonomic (especially vagal) reflexes, reduction of airway secretions, amnesia, prophylaxis against pulmonary aspiration of gastric contents, facilitation of induction of anesthesia, and possible analgesia and to potentially mitigate the stress response and prevent malignant cardiac arrhythmias [18].
A list, although not necessarily exhaustive, of the main indications for premedication in children includes:
Children/teenagers who already show a high degree of anxiety
Children who cannot be separated easily from the parent
Cases in which the anesthesiologist thinks that PPIA is not of benefit
Children with previous experience of surgery, perhaps characterized by a negative memory or discomfort
Children with neurological and behavioral disorders
Children with comorbidities requiring smooth induction, possibly without crying or agitation (e.g., patients with cardiac disease)
Before examining the most frequently used drugs for premedication, it should be noted that its risks are respiratory depression, loss of airway reflexes, paradoxical response to the drug, and obviously potential allergic reactions. These risks are generally influenced not only by age but also by underlying medical conditions (furthermore in this chapter, we refer to elective surgery, but there are special circumstances such as full stomach, head or abdominal trauma, etc., that require different considerations). Although risks are mainly connected to a relative overdose (or coadministration of another drug) and can therefore be minimized using a high degree of attention, the conditions that may require close monitoring after premedication are:
Upper airway obstruction and/or obstructive sleep apnea syndrome
Neurological disorders
Dysphagia or gastroesophageal reflux
Infants
Heart disease (especially cyanotic heart defects)
The goal of premedication in children should be individualized: a mild sedation, while not able to eliminate anxiety completely, can be effective in a child who is not very agitated and could therefore make the induction mild and pleasant. Conversely, a heavier sedation may be necessary in the case of a very agitated child.
The factors to be considered when choosing the drug(s) are therefore age, weight, medication history of the patient (allergies), comorbidities, expectations of the child and family, level of psychological maturity, anxiety, and cooperativeness.
Another important point to consider is the route of administration of the drug. Although parenteral administration (especially intravenous) can be faster, can be more effective, and have a greater predictability in terms of clinical response, the majority of pediatric anesthesiologists refrain from this route of administration unless there is a venous access in place. In fact, most of the children reported needle puncture as their worst experience in hospital.
For this reason, enteral or transmucosal premedication is better accepted by the child, parents, and hospital staff. A noteworthy exception to this general rule (according to the experience of the authors) is for children born with spina bifida who generally do not have sensitivity in the buttock region. The same children on the other hand are often hostile to inhalation induction, often already have experience during previous surgeries. The doses of the two main drugs (midazolam and ketamine) used intramuscularly as premedication in Italy are disclosed in Table 3.1.
Table 3.1
Drugs and doses commonly administered for premedication
Drug | Route | Dose (mg/kg) |
---|---|---|
Midazolam | Oral | 0.3–0.7 (up to 20 mg) |
Nasal | 0.2 | |
Rectal | 0.5–1 | |
Intramuscular | 0.1–0.15 | |
Ketamine | Oral | 3–8 |
Nasal | 3–6 | |
Rectal | 5–10 | |
Intramuscular | 2–5 | |
Clonidine | Oral | 0.002–0.004 |
Nasal | 0.002–0.004 | |
Rectal | 0.002–0.005 | |
Dexmedetomidine | Oral | 0.001–0.004 |
Nasal | 0.001–0.004 |
In spite of the relative abundance of literature about the different drugs/routes of administration, we can state that the ideal drug (or the ideal combination of drugs) for premedication in children has unfortunately yet to be invented. In this brief review, we will focus on oral, nasal, and rectal routes by examining midazolam, α-2 agonists, and ketamine.
3.2.1 Oral Route
Although the oral route of administration does not always produce predictable and consistent effects because of fluctuations in the bioavailability and a substantial first-pass effect, it still remains the most accepted and widespread way of administration [19].
Although in the past it was feared that oral premedication might increase gastric residual volume and therefore increase the risk of reflux with subsequent inhalation, this was later denied, as long as a large amount of fluid is not ingested [20].
3.2.1.1 Midazolam
Midazolam administered orally still remains the method of choice in 90% of cases in the USA according to a recent survey [21]. The usual dose of 0.5 mg/kg up to a maximum of 20 mg causes a constant anxiolysis in the presence of a large safety margin, whereas the increase above 0.5 mg/kg does not result in an increase of its sedative or anxiolytic properties [22]. The sedative and anxiolytic effect starts after 10’ and is present after 20’ in the vast majority of children [23]. The peak effect is observed at 30’, but after 45’ the effect on separation anxiety starts to disappear [24], even with a possible sedative/light anxiolytic effect up to 2 h.
The effect on awakening times seems to be minimal, while there have been conflicting data on discharge time over years. A recent review [25] has shown that premedication with midazolam 0.5 mg/kg 30’ before surgery reduces separation anxiety at induction but does not increase recovery times, while opposite results were found in a previous study [26].
It is essential for the anesthesiologist to be careful about the timing of midazolam administration to prevent the child from arriving in the operating room not properly sedated (due to either a late or an early administration). In this last case, however, a re-administration of midazolam at a reduced dose (e.g., 0.25 mg/kg) can be attempted.
The main problem of oral midazolam is its bitter taste. In 1998, the FDA approved a syrup with a more pleasant taste and a lower pH than the intravenous formulation, thus increasing its bioavailability. A coadministration with a more pleasant tasting syrup may be useful.
In another study, oral midazolam did not result in an increased frequency of delirium and agitation after awakening [26]. On the other hand, the effects on behavioral outcomes such as nightmares, nocturnal enuresis, etc., are contradictory. Doses greater than 0.5 mg/kg are associated with side effects such as alterations in balance, posture, vision, and dysphoric reactions in the postoperative period [26]. Of note, these reaction can easily be controlled and antagonized by the administration of flumazenil 10 μg/kg up to 1 mg iv.
Midazolam (0.5 mg/kg) has been compared to clonidine (4 μg/kg) for premedication in children undergoing tonsillectomy and has been found to be better in terms of preoperative anxiety and postoperative analgesia, with no difference in awakening and discharge times [27]. When compared to oral ketamine 5 mg/kg, midazolam has displayed similar effects but with a better recovery and discharge profile [28]. Similarly, a better sedation and anxiolysis has been observed with midazolam (0.5 mg/kg) compared to the combination diazepam-droperidol (0.25 mg/kg each) [29]. After sevoflurane anesthesia, midazolam was found to be as effective as clonidine and melatonin in reducing postoperative agitation [30].
3.2.1.2 Ketamine
Despite its marked first-pass effect, the usual dose of 6 mg/kg makes the children quiet and calm at the time of separation from their parents within 30’ and provides good conditions at the time of induction [31]. Oral ketamine does not generally produce effects like tachycardia, respiratory depression, agitation during awakening, or nightmares [23], even though episodes of hallucinations and laryngospasm have been reported [32].
3.2.1.3 α2-Agonists
In recent years, there has been a sort of “rediscovery” of α2−agonists although clonidine has been used for years for premedication in children. It has anxiolytic, sedative, and analgesic properties, tastes better than midazolam, and displays a high rate of satisfaction among both the medical care team and parents.
Clonidine results in sedation, amnesia, perioperative hemodynamic stability, and intraoperative (in terms of reduction of anesthetics) and postoperative analgesia, when orally administered at the dose of 1–4 μg/kg. In addition, premedication with clonidine 4 μg/kg before adenotonsillectomy was as effective as the administration of fentanyl 3 μg/kg perioperatively as far as postoperative analgesia (VAS and morphine consumption) was concerned [33]. The effectiveness of premedication with clonidine in reducing postoperative pain has been confirmed by a Cochrane meta-analysis in 2014 [34].
Due to its pharmacodynamic effect, clonidine produces a state of sedation more similar to fatigue and physiological sleep when compared to midazolam. This is also demonstrated by the ability of patients to be easily awakened to perform a variety of cognitive tests [35, 36].
One of the disadvantages of premedication with clonidine is its markedly delayed onset, up to 90’. Still, many pediatric anesthesiologists accept this delay as it is largely offset by its beneficial perioperative clinical effect. In particular, what is valued and desirable in pediatric anesthesia is its reduction of sympathetic outflow without the simultaneous reduction of compensatory homeostatic reflexes. In fact, although bradycardia and hypotension are potentially dangerous side effects, they do not actually occur if the total dose of clonidine is below 10 μg/kg.
The more recently introduced dexmedetomidine is an α2-agonist with an α2/α1 specificity eight times greater than clonidine (1600:1 vs. 200:1). This greater selectivity, together with its limited cardiorespiratory effects, could theoretically offer some advantages even though data are still limited. Preliminary and retrospective data indicate that dexmedetomidine can be used for both premedication and procedural sedation at a dose of 1–4 μg/kg [37]. An important paper comparing premedication with oral midazolam(0.5 mg/kg), oral clonidine (4 μg/kg), and transmucosal dexmedetomidine (1 μg/kg) showed no difference in terms of anxiety and postoperative sedation but greater intraoperative hemodynamic stability and reduced postoperative pain in the clonidine and dexmedetomidine group compared to midazolam [38].
3.2.2 Nasal Route
The drugs most frequently administered through the nasal route are midazolam, ketamine, and more recently dexmedetomidine.
Nasal absorption is usually faster than the oral route. It is generally true that any side effects (such as respiratory depression) could occur more rapidly, and therefore, this route of administration should only be used when there is personnel with equipment readily available to intervene.
Traditionally premedication through the nasal route included both drops and sprays. Considering the widespread diffusion of devices such as atomizers, nowadays sprays seem more widespread than drops. For this reason, a proper and precise dose must be administered to generate a rapid and predictable onset. The only real disadvantage of nasal sprays is the possible uncomfortable feeling for patients which can sometimes be associated with anxiety and fear, even though the discomfort linked to nasal administration of midazolam can be reduced by pre-administration of a lidocaine puff.
3.2.2.1 Midazolam
At the dose of 0.2–0.3 mg/kg, nasal midazolam has proven effective in the reduction of separation anxiety and during induction, while not increasing recovery and discharge times even after short surgeries. In a direct comparison between 0.2 mg/kg and 0.3 mg/kg, the higher dose resulted in a higher efficacy without an increase in side effects [39].
Nasal midazolam (0.5 mg/kg) has been compared to a combination of ketamine-midazolam and has proven as effective as the combination in reducing separation anxiety in all patients even if its effect took twice as much time (5 min vs. 2.5 min) as the combination of drugs [40].