Professor Zhang Hui: Do Anesthetic Drugs Affect Children's Intelligence? How to Choose Between General and Regional Anesthesia?

Professor Zhang Hui: Do Anesthetic Drugs Affect Children's Intelligence? How to Choose Between General and Regional Anesthesia?

Source: Sunflower Children Author: Zhang Hui Editor: Yangyuan Date: December 31, 2023

Children with hematological cancers often undergo procedures like bone marrow aspiration, lumbar punctures, and sometimes even abdominal and thoracic punctures, along with surgeries, all of which can cause them pain.

"Little pain equals motivation," and "Can children (especially newborns) feel pain?" are common questions we hear in clinical settings. Many parents, when faced with the prospect of pain, prefer to have their children "tough it out" rather than accept proactive interventions. This "pain tolerance culture" highlights the urgent need to improve public understanding of pain.

In fact, procedures done under sedation or analgesia can alleviate physical pain and psychological stress in children, allowing both the patients and their parents to approach treatment more positively, enhancing treatment efficiency and experience, and improving the overall treatment environment.

Despite this, many parents still have concerns about sedation and analgesia, and we hope this article will help alleviate some of those doubts.

Can Children Feel Pain?

Many parents wonder, "Can children (especially newborns) feel pain?" and often ask doctors, "Is it possible to avoid anesthesia or sedation?"

It is important to clarify that children, even infants, can indeed perceive pain and respond to it with a range of physiological reactions. Negative memories of pain during childhood can affect a child's future life. Without anesthesia or sedation, the painful experiences and memories associated with clinical procedures can last a lifetime, potentially leading to social and psychological issues in children, such as tendencies toward violence.

The International Association for the Study of Pain (IASP) defines pain as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage." According to this comprehensive definition, pain is far more than just physical injury. The term "total pain," first coined by Cicely Saunders, encompasses physical, emotional, social, and spiritual aspects of pain.

Despite the high prevalence of pain, it is often underestimated and inadequately treated in infants, children, and adolescents, especially those with cancer.

This underestimation and lack of treatment reflect various long-held misconceptions, such as: infants do not feel pain; they do not remember painful experiences; children experience less pain than adults; fear of medication use; children are more prone to opioid addiction than adults...

Such misconceptions lead to delayed pain management for children and overly cautious administration of sedatives and analgesics, causing unnecessary suffering. In reality, children's pain perception is not less than that of adults.

The origin of anesthesia can actually be traced back to ancient China with Hua Tuo's invention of "Mahuosan," although evidence of this drug's existence is lacking. In 1846, Dr. Morton demonstrated ether anesthesia at Massachusetts General Hospital, while prior to this, Dr. Long had already begun performing clinical anesthesia, with his second case being a child. Although the history of pediatric anesthesia is not short, its development has significantly lagged behind that of adult anesthesia.

Compared to adults, the routes of administration for pediatric sedation and anesthesia are diverse, including intravenous, inhalation, rectal, nasal, subcutaneous or intramuscular injections, and others, such as epidural administration (including caudal anesthesia), subarachnoid administration, and nerve blocks. Among these, intravenous and inhalation methods are more commonly used in pediatric anesthesia.

The metabolism of sedative and anesthetic drugs in children cannot be generalized; children are not just smaller versions of adults. The factors determining drug effects in children are both diverse and complex, as drug absorption, distribution, metabolism, and elimination processes differ from those in adults. Therefore, sedation or anesthesia in children should be conducted with the assistance of pediatric anesthesiologists.

Do Sedatives and Anesthetic Drugs Affect Children's Intelligence?

Many parents' concerns about anesthetic drugs seem to stem from a 1999 paper published in Experimental Neurology, which found increased apoptosis of cortical cells in newborn mice after the use of NMDA receptor antagonists (with ketamine being a commonly used drug in this category), potentially affecting neural development.

Subsequently, a 2003 study published in The Journal of Neuroscience found that new rats exposed to midazolam, nitrous oxide, and isoflurane anesthesia for six hours showed impaired physiological functions in a specific area of the hippocampus (a brain region associated with learning and memory), leading to spatial cognitive deficits in the rats at four weeks to four months of age.

These studies quickly garnered significant attention in the field of anesthesiology and society at large—are the concerns valid?

There are several important points to note: 1) The experimental dosages used were far greater than those typically applied in clinical practice. For example, the dosage of ketamine was as high as 20–100 mg/kg, while the clinical dosage is 2 mg/kg; isoflurane was used at doses of 10–60 mg/kg, whereas the clinical dosage is 1 mg/kg; and midazolam was used at doses above 9 mg/kg, while the common clinical dose is 0.1 mg/kg. 2) No causal relationship has been established between sedation/anesthesia and neuronal apoptosis or the development of learning and memory in humans.

Additionally, human learning and intelligence are influenced by multiple factors, so unless we have twins raised in nearly identical environments—one undergoing anesthesia and the other not—the results would be more persuasive (though even in twins, learning abilities may not be identical).

Existing retrospective analyses have confirmed that sedation and anesthesia do not affect children's learning abilities and cognitive development. In 2007, the U.S. Food and Drug Administration (FDA) advisory committee concluded, "Based on current evidence, there is no need to change the status quo in clinical anesthesia." In 2013, expert opinions stated, "Even if anesthesia has a slight impact on the nervous system, changing the existing anesthesia techniques for children or avoiding anesthesia altogether could pose a greater risk to the nervous system."

While sedation and anesthesia do not affect intelligence, parents should also be aware of potential adverse reactions associated with the drugs. Possible adverse effects following sedation and anesthesia include allergies, respiratory depression, nausea, vomiting, itching, agitation, and chills. Parents need to remain vigilant and report or handle any issues promptly.

If a child experiences an allergic reaction or respiratory depression, it is crucial to inform medical staff immediately. Nausea and vomiting after surgery are quite common, but most often, they subside over time. In severe cases (such as frequent vomiting or retching), it is important to seek timely medical assistance. When a child vomits, ensure their head is turned to the side to prevent aspiration, especially into the lungs. Itching may accompany allergic reactions; if the severity is mild, it usually requires no treatment. Postoperative agitation is common, and children may be extremely uncooperative, but they typically recover gradually over time. After sedation or anesthesia, key points to monitor include whether the child’s consciousness has returned, if their breathing is stable (compared to pre-operative conditions), and whether their skin color appears normal.

In summary, postoperative care requires the joint efforts of parents and healthcare professionals to ensure the child's physical recovery.

Can a Quiet Child Do Without Anesthesia?

"My child is usually very obedient; I'm worried about the potential negative effects of anesthesia. Since this is just a minor surgery, can we skip the anesthesia?" This is a question many parents have.

It's understandable for parents to worry for their children's well-being. However, forgoing anesthesia can have lifelong implications. A child may become overly sensitive to pain due to this surgery, leading to lasting psychological fears and trauma.

Consider this: many people around us have undergone general anesthesia for procedures like endoscopies and cesarean sections without any lasting side effects. Yet, a conscious endoscopy can leave many feeling psychologically traumatized afterward.

Is General Anesthesia Too Much? If Possible, Should We Choose Regional Anesthesia?

"Will general anesthesia for a newborn affect their neurological development?" "I've heard that children who have surgery at a young age may be slow to respond when they grow up." Many parents have such concerns.

Is general anesthesia really that scary? The decision to use general anesthesia, regional anesthesia, or local anesthesia primarily depends on clinical indications and contraindications, as well as the patient's physical condition and the surgical site. General anesthesia affects the entire body by influencing the central nervous system, causing loss of consciousness and complete pain relief. It is effective for pain management and is applicable to a wide range of surgical procedures.

If a child is very young and only local anesthesia is used, while the surgical site may not experience pain, the child may still feel discomfort due to stretching or stimulation during the procedure, making cooperation difficult.

Moreover, even during a wound cleaning operation, if the surgery is performed while the child is conscious, they will inevitably experience psychological fear, which may lead to movement and struggle, adversely affecting the procedure. In such cases, general anesthesia is recommended. For school-aged children over seven years old who can cooperate, regional or local anesthesia may be considered.

References:

[1] Cancer pain management guidelines issued for children; adult guidelines updated. JNCI-J NATL CANCER I. 2005-05-18;97(10):711-2.

[2] N-Methyl-aspartate Receptor Blockade Induces Neuronal Apoptosis in Cortical Culture. Exp Neurol. 1999 Sep;159(1):124-30.

[3] Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits. J Neurosci. 2003 Feb 1;23(3):876-82.

Author: Zhang Hui

International Children's Medical Center, Shanghai Children's Medical Center, Fujian Hospital

Director of Hematology Oncology

Layout: Xia Yu