Drug
Weight used for dosing
Propofol
Induction
IBW
Maintenance
TBW
Fentanyl
TBW
Sufentanil
TBW
Remifentanil
IBW
Alfentanil
IBW
Morphine
IBW
Midazolam
TBW
Rocuronium
IBW
Vecuronium
IBW
Succinylcholine
TBW
Genetic, Phenotypic, and Cultural Differences
Numerous genetic polymorphisms lead to individual patient variations in enzyme activity. These variations alter responses to anesthetics and adjuncts used perioperatively. A common polymorphism is the genetic mutation leading to a dysfunctional form of the enzyme pseudocholinesterase which is responsible for the metabolism of succinylcholine [10]. Often found incidentally in the operating room, a single dose of succinylcholine may result in prolonged decreased muscle strength [10]. If suspected, then the patient should be tested with findings reported to future anesthesia providers. Another genetically mediated complication associated with succinylcholine is malignant hyperthermia (MH) [11]. Once identified, prompt treatment with dantrolene and the avoidance of further exposure to “triggers” (volatile anesthetics and succinylcholine) can be lifesaving [11]. Additional perioperative drugs are subject to genomic polymorphisms which may alter their efficacy and safety. One example is codeine whose action is primarily dependent on the metabolism to its active metabolite, morphine. CYP2D6, the cytochrome P450 enzyme responsible for the conversion of codeine to morphine, is associated with genetic polymorphisms that range from “poor metabolizers” who get little analgesic effect to “ultrarapid metabolizers” who are at risk for opioid toxicity. Unfortunately, there is no reliable phenotype that identifies to which group a patient belongs, so judicious use is recommended especially in those naïve to the drug [12].
Ethnic and physical phenotypic characteristics have been associated with changes in anesthesia requirements perioperatively. One phenotype shown to change anesthetic requirement perioperatively is red hair. These patients have a higher than expected minimum alveolar concentration (MAC) [13]. Other differences among patients may be cultural rather than genetic. Lower negative behavioral changes (including anxiety, apathy, and eating disturbances) are reported by Spanish-speaking Hispanics when compared to English-speaking whites [14]. These findings are important for the anesthesia provider to consider as suboptimal treatment may take place if these subtle characteristics are ignored [14].
Cardiovascular Medications
Hypertension is one of the most common diseases in the United States [15], and antihypertensive therapy is often prescribed. The anesthetic implications of this group of medications are numerous and mainly positive. This is appreciated when one examines the mortality reduction seen in high-risk patients who maintain beta-blocker and/or alpha-2 agonist therapy into the perioperative period [16, 17]. Alpha-2 agonists also have analgesic, sedative, and anti-shivering properties, which lower anesthetic requirements [18]. However, signs of hypovolemia and/or anemia may be masked by the drugs blunting of the normal compensatory sympathetic discharge mechanism. As a result, the anesthesia provider may fail to recognize intravascular volume depletion [19]. Investigation into the length of administration, compliance, and the timing of the patient’s last dose is an important part of the preassessment. A patient may become tachycardic or severely hypertensive if either beta-blockers or alpha-2 agonists are abruptly discontinued. This rebound effect must be considered by the anesthesia provider in the differential for tachycardia or hypertension in the perioperative period [20].
Other antihypertensive medications commonly used include the angiotensin receptor blockers (ARB), angiotensin-converting enzyme (ACE) inhibitors, and diuretics. These drugs deplete intravascular volume which may increase hypotensive episodes shortly after the induction of general anesthesia – necessitating the need for more vigorous fluid resuscitation intraoperatively [21]. Furthermore, some diuretics (i.e., thiazides and loop diuretics) can cause hypokalemia leading to hyperpolarization of the neuromuscular membrane and, thus, potentiating the effects of non-depolarizing neuromuscular blockers [22]. The effects of these medications should be considered in the anesthetic plan.
Pulmonary Meds
Asthma affects millions in the United States [23]. Inhaled bronchodilators, including beta-2 agonists and anticholinergics, are often prescribed for the asthmatic. Side effects include tachycardia, but the benefits far outweigh the risks. First, both inhaled beta-2 agonists and anticholinergics have been shown to decrease perioperative pulmonary complications and should be continued into the perioperative period [24]. Second, the duration of treatment and frequency of use of these medications may indicate disease severity allowing for adjustments to the anesthetic plan.
Corticosteroids (both oral and inhaled) are prescribed for asthma and chronic obstructive pulmonary disease (COPD). Like bronchodilators, patients should continue their inhaled corticosteroids perioperatively to reduce pulmonary complications [25]. Maintenance of steroid therapy also reduces the incidence of acute adrenal insufficiency due to suppression of the hypothalamic-pituitary-adrenal (HPA) axis from chronic steroid use [26, 27]. A commonly used intravenous anesthetic agent, etomidate, can cause adrenal suppression and is best avoided with long-standing corticosteroid therapy [28]. Because of its cardiovascular stability, its use may be unavoidable, and patients should be monitored for signs of adrenal insufficiency and receive additional steroids [29]. “Stress dosing” of asthmatic patients taking oral steroids (the intravenous administration of the normal daily requirement, approximately 150 mg of hydrocortisone in divided doses) is controversial and depends upon many factors including therapy duration, route of administration, and dose of corticosteroid as well as degree of surgical stress expected [30, 31]. An additional stress dose of corticosteroids should be provided to patients who are on replacement therapy for primary adrenal insufficiency. Patients without primary adrenal insufficiency who have taken a therapeutic dose of steroids on the day of surgery may be observed and given additional corticosteroid as necessary [32]. Supplemental perioperative steroids are not indicated for patients on inhaled corticosteroids.
Estrogen-Containing Medications
Surgery is a known risk factor for thromboembolic events [33]. The anesthetic implications of estrogen-containing medications include their propensity to further increase this risk [34]. Estrogen is commonly found in oral contraceptive pills (OCPs) and hormone replacement therapy (HRT). Selective estrogen receptor modulators (SERMs) act at the estrogen receptor and carry the same risk as the former two classes of estrogen-containing drugs. Patients undergoing procedures associated with a high risk for thromboembolic events may benefit from discontinuing estrogen-containing medications preoperatively – at least 6 weeks prior to surgery [35]. However, this may be difficult for patients on OCPs without other means of birth control and for those on SERMs for treatment of breast cancer. A discussion with the surgeon regarding the risks and benefits of discontinuing these medications preoperatively may be warranted.
Antiplatelets
Many patients with peripheral arterial disease (PAD) are prescribed antiplatelet medications. These agents decrease thromboembolic events, particularly in patients undergoing coronary artery bypass and surgery for PAD [36]. The two commonly used classes of antiplatelet medications are cyclooxygenase inhibitors (i.e., aspirin) and P2Y12 inhibitors (i.e., clopidogrel). If a patient is taking aspirin, the risks and benefits of continuing aspirin perioperatively should be weighed. The risk is increased bleeding intraoperatively, while the benefit is a reduced risk of thromboembolism. Unless a bleeding complication would yield catastrophic results as with surgeries involving the posterior chamber of the eye, middle ear, and intracranial and intramedullary spine, patients who are at a moderate risk for cardiovascular thrombotic events in the perioperative period should continue taking aspirin [37]. Neuraxial blocks are not contraindicated in patients on aspirin [38]. If aspirin must be discontinued, it should be done 7 days prior to surgery to ensure its effects have receded.
P2Y12 receptor blockers such as clopidogrel and ticlopidine are commonly used in patients with coronary stents. After stent placement, dual antiplatelet therapy is required for a minimum duration during which time discontinuation of the medications can increase risk of stent thrombosis [37]. Elective surgery should be delayed as stent thrombosis is a catastrophic complication [37]. When the risk of hemorrhage outweighs the benefits of P2Y12 blocker therapy and the surgical procedure is urgent or emergent, P2Y12 receptor blockers should be stopped briefly and resumed shortly thereafter [39]. Ideally, in order to fully regain platelet function, clopidogrel should be stopped for at least 7 days and ticlopidine stopped for at least 14 days prior to surgery [40]. These patients may benefit from multidisciplinary management involving the anesthesia providers and the patients’ cardiologist and surgeon. Neuraxial blocks are contraindicated in patients taking P2Y12 receptor antagonists due to the high risk for developing epidural hematomas and can only be safely used if the drug is stopped for a sufficient time for platelet function to be regained [41].
Psychotropic Medications
Antidepressants
Antidepressant medications are a commonly used class of medications and carry significant anesthetic implications. Most common and severe are the interactions seen with the use of vasopressors. The main classes of antidepressants in common use are tricyclic antidepressants (TCAs), serotonin reuptake inhibitors (SSRIs), and monoamine oxidase (MAO) inhibitors. TCAs work by inhibiting norepinephrine and serotonin uptake at the synaptic cleft. Intuitively, concomitant perioperative use of sympathomimetic drugs could lead to an exaggerated sympathetic response [42]. Therefore, the use of direct and indirect sympathomimetic drugs should be carefully titrated and monitored. Furthermore, anesthetic agents that can augment sympathetic activity (e.g., ketamine, pancuronium) should be used with caution. MAO inhibitors prevent the enzyme monoamine oxidase from metabolizing catecholamines. Secondarily, administration of indirect sympathomimetics to patients taking this class of antidepressants can lead to a massive and life-threatening catecholamine surge [43]. In addition, MAO inhibitors administered with meperidine increases the risk of serotonin syndrome, presenting as agitation, headaches, fever, seizures, and possibly coma and death. Further, abrupt cessation of TCAs can cause withdrawal symptoms, while cessation of either MAO inhibitors or TCAs can precipitate acute depressive episodes. Serotonin reuptake inhibitors (SSRIs) inhibit serotonin reuptake at synaptic clefts. SSRIs have anesthetic implications by way of their antiplatelet actions causing potential for increased blood loss intraoperatively. Conversely, the antiplatelet activity carries potential protective effects in patients with ischemic heart disease [44].
Mood Stabilizers and Antipsychotics
These classes of medications are seen in patients with severe psychiatric illnesses. The major mood-stabilizing medication with significant anesthetic implications is lithium which is the treatment of choice for bipolar disorder. Complications of lithium therapy include nephrogenic diabetes insipidus and hypothyroidism [45, 46]. Investigation for these conditions should be considered preoperatively as both of these complications have major perioperative implications. Furthermore, lithium potentiates the effect of non-depolarizing neuromuscular junction blockers, and their use should be carefully titrated in these patients [47]. Conversely, valproic acid (sometimes used as second line treatment for bipolar disorder) antagonizes non-depolarizing muscle relaxants necessitating increased dosing [48].
Many antipsychotic medications work by inhibiting dopaminergic transmission in the brain [49]. Both first- and second-generation antipsychotics are associated with an increased risk of sudden death when taken in the perioperative period [50]. This may be secondary to the increased risk of arrhythmias associated with the QT prolongation seen with the use of these medications – especially when used in conjunction with volatile anesthetics and some antibiotics such as quinolones and erythromycin [51, 52]. Despite these concerns, cessation of antipsychotics preoperatively may not be a feasible option in some as acute withdrawal from antipsychotics can precipitate psychoses or the neuroleptic malignant syndrome [53]. This provides a challenge for the anesthesia provider, and thus consultation with a psychiatrist is recommended preoperatively.
Opioids
Patients who chronically take opioids will develop tolerance to their analgesic effects. These patients will thus require higher doses of analgesics in the perioperative period [54]. Preoperatively, these patients are advised to maintain opioid use to optimize perioperative care and avoid withdrawal symptoms [55]. The use of adjuvant analgesic therapy as well as regional techniques may be invaluable in the perioperative care of these patients. Obtaining a preoperative pain management consult to guide perioperative pain regimen may help improve postoperative patient recovery and satisfaction. Tolerance to some opioid effects is not observed (e.g., miosis, constipation). Therefore, using pupil size in an anesthetized patient to determine the degree of narcosis is still plausible in these patients [56].
Herbal Medications
Herbal medications are becoming an increasingly important part of medical care of patients. Common herbal remedies include ephedra, garlic, ginkgo, ginseng, kava, St. John’s wort, valerian, and echinacea. All these herbal medications have associated side effects that impact the perioperative care of patients. Table 5.2 enumerates the side effects and anesthetic concerns with commonly encountered herbal medications. Of note, there are no reported benefits to the use of herbal medications in the perioperative period. In fact, there are reports of increased morbidity, and it is generally recommended to stop the use of herbal medications 2–3 weeks prior to elective surgery given that the half-life of these agents in any single preparation is typically unknown [57].
Table 5.2
Herbal medication or remedy and its potential effects and implication on the anesthetic plan
Herbal remedy | Associated effect and anesthesia implication |
|---|---|
Ephedra | Increase in risk for myocardial infarction and stroke – should be stopped at least 24 h preop. It should be considered a less pure and natural ephedrine |
Garlic | Increases bleeding risk – should be stopped at least 7 days preop |
Ginkgo | Increases bleeding risk – should be stopped at least 36 h preop |
Ginseng | Can precipitate hypoglycemia, increase bleeding risk – should be stopped at least 7 days preop |
Kava | Has sedative effects and can decrease mood with association of depression. Coadministration with sedatives such as benzodiazepines and barbiturates can enhance sedation. Dozens of reported cases of kava-mediated liver injury, including fatal hepatotoxicity |
St. John’s wort
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