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Address reprint requests to Michael J. Murray, MD, PhD

Mayo Clinic Rochester, MN 55905

Guest Editor's Commentary Perioperative Pharmacology

"An understanding of the basic pharmacokmetic and pharmacodynamic principles is important in managing drug therapy in any patient population, particularly so in patients

treated in an operating room or admitted to an ICU. . . Therefore, dosing of medications to critically ill patients needs to be based on therapeutic drug monitoring, or, as is most commonly done in the ICU, through the adjustment of a continuous intravenous infusion,

monitoring the patient for attainment of the desired therapeutic effect."

MICHAEL J. MURRAY, MD, PhD

PERIOPERATIVE PHARMACOLOGY 795

The pharmacology of the perioperative period is complicated both by the anticipated actions of anesthetic drugs on the metabolism and on their potential interactions with the patient’s pre-existing pharmacother- apy and chronic organ system dysfunction. Murray’s discussion pro- vides insight into the anesthesiologist’s role as a perioperative clinician pharmacologist in bridging the therapeutic gap between the operating room, postoperative recovery unit, and ICU. Although the discussion focuses appropriately on the scientific principles underpinning drug action, metabolism, and excretion, the anesthesiologist’s critical role as a clinician pharmacologist is highlighted by the recognition that a patient’s normal responses to conventional therapy are altered by requisitely administered anesthetic agents. Such agents possess, characteristics that compromise cardiac output and distribution of organ blood flow, de- press consciousness, decrease intrinsic metabolic processes, and alter body water homeostasis. They also may employ extraorgan metabolic pathways that are independent of normal drug metabolism and there- fore outside the experience of nonanesthesiologists.

Equally important is understanding the concepts of bioavailability, volume of distribution, and clearance prior to a discussion relevant to choosing an appropriate drug administration route. Intravenous, inhala- tion, transdermal, transbuccal, and oral routes are all available and of varying utility and appropriateness perioperatively. In addition, drug formulation and administration problems are common in ICU practice and doses must be adjusted if full therapeutic benefit is to achieved. In the operating room, for example, inhalation agents are titrated to the endpoint of patient response to surgical insult yet, in the ICU, even though it is known that concentrations of inhaled bronchodilators are decreased when administered through a ventilator nebulizer, dosing is commonly prescribed in the conventional manner that presupposes delivery of the total metered dose to the alveolar/capillary exchange area.

Chronic disease, with associated organ dysfunction, suggests a role for anesthesiologists outside the operating room. Few physicians are as accustomed to dealing with multiple drug interactions on an acute basis as are anesthesiologists. The managed care paradigm will force acceptance of the concept that medical care must be administered cost effectively in an environment favoring cross-functional patient manage- ment rather than in the current, vertically integrated, specialty-dominant model. The postoperative patient requires continuous, effective titration of increasingly expensive drugs targeted to produce documentable re- sults rapidly. The anesthesiologist possesses the knowledge and experi- ence to function effectively in this milieu. As noted elsewhere, however, the change in emphasis will be neither easy nor natural for many anesthesiologists accustomed to the operating room, and increased focus on critical care medicine and pain management programs, in addition to new courses in administration and management, will be necessary for today’s practitioners and new graduates to acquire the requisite

796 LUMB

professional and personal skills to compete in these extended aspects of patient care.

The perioperative period is marked by physiologic instability, al- tered metabolic responses and de fact0 changes in anticipated drug distribution and metabolism, reduced effectiveness of host immune de- fenses, initiation and escalation of the patient’s intrinsic stress response, and varying degrees of major organ system dysfunction that depend upon the acute insult and underlying chronic illness. It should be of minimal surprise that drug administration and subsequent effect are equally compromised by alterations in drug volume of distribution and binding characteristics, metabolism, and excretion. In addition, drug- drug interactions acquire new importance and specific mechanisms of administration may differentiate effectiveness among varying classes of drugs, requiring differential approaches to drug titration and monitor- ing. Successful, cost-effective management of the perioperative patient requires both meticulous attention to the details of anesthetic and surgi- cal technique and careful surveillance of the drugs used to control all aspects of the patient’s pharmacologic course. Professional and societal behavioral issues will become obvious as sophistication and manage- ment increase in perioperative medicine. Pharmacologic choice impacts upon hospital budgets, and careful justification of expenditures will be required. Formulary acquisition of new drugs will be possible only if the pharmacologic promise matches the observed therapeutic effect. As discussed elsewhere, that may also require behavioral change on the part of health care professionals and patients, but for the purposes of this discussion, the focus remains on the correct administration of agents, new and old alike, which assumes a deep understanding of the pharma- cokinetic principles that guide pharmacodynamic effects. The specialized education, developed clinical acumen, and organized observational skills of the anesthesiologist make for an unrivaled opportunity to extend practice limits outside the operating room into the perioperative arena in which those talents will be required if institutions, practices, and patients are to survive the rigors of bottom-line medicine.

PHILIP D. LUMB, MB, BS Guest Editor