Audrey Shafer

Pharmacokinetics and pharmacodynamics of propofol infusions during general anesthesia

The pharmacokinetic and pharmacodynamic properties of propofol were studied in 50 surgical patients. Propofol was administered as a bolus dose, 2 mg/kg iv, followed by a variable-rate infusion, 0–20 mg/min, and intermittent supplemental boluses, 10–20 mg iv, as part of a general anesthetic technique that included nitrous oxide, meperidine, and muscle relaxants. For a majority of the patients (n = 30), the pharmacokinetics of propofol were best described by a two-compartment model. The propofol mean total body clearance rate was 2.09 ± 0.65 1/min (mean · SD), the volume of distribution at steady state was 159 ± 57 I, and the elimination half-life was 116 ± 34 min. Elderly patients (patients older than 60 yr vs. those younger than 60 yr) had significantly decreased clearance rates (1.58 ± 0.42 vs. 2.19 ± 0.64 1/min), whereas women (vs. men) had greater clearance rates (33 ± 8 vs. 26 ± 7 1 · kg−1 · min−1) and volumes of distribution (2.50 ± 0.81 vs. 2.05 ± 0.65 1/kg). Patients undergoing major (intraabdominal) surgery had longer elimination half-life values (136 ± 40 vs. 108 ± 29 min). Patients required an average blood propofol concentration of 4.05 ± 1.01 μg/ml for major surgery and 2.97 ± 1.07 μg/ml for nonmajor surgery. Blood propofol concentrations at which 50% of patients (EC50) were awake and oriented after surgery were 1.07 and 0.95 μg/ml, respectively. Psychomotor performance returned to baseline at blood propofol concentrations of 0.38–0.43 μg/ml (EC50). This clinical study demonstrates the feasibility of performing pharmacokinetic and pharmacodynamic analyses when complex infusion and bolus regimens are used for administering iv anesthetics.

Complications of sedation with midazolam in the intensive care unit and a comparison with other sedative regimens

OBJECTIVE To describe the various complications that have been reported with use of midazolam for sedation in the intensive care unit (ICU). DATA SOURCES Publications in scientific literature. DATA EXTRACTION Computer search of the literature. SYNTHESIS Sedation is required in the ICU in order for patients to tolerate noxious stimuli, particularly mechanical ventilation. Under- and oversedation can lead to complications. To sedate patients in the ICU, midazolam is commonly administered via titrated, continuous infusions. Cardiorespiratory effects tend to be minimal; however, hypotension can occur in hypovolemic patients. Prolonged sedation after cessation of the midazolam infusion may be caused by altered kinetics of the drug in critically ill patients or by accumulation of active metabolites. In addition, paradoxical and psychotic reactions have been rarely reported. Tolerance and tachyphylaxis may occur, particularly with longer-term infusions (> or = 3 days). Benzodiazepine withdrawal syndrome has also been associated with high dose/long-term midazolam infusions. Compared with propofol infusions, midazolam infusions have been associated with a decreased occurrence of hypotension but a more variable time course for recovery of function after the cessation of the infusion. Lorazepam is a more cost-effective choice for long-term (> 24 hrs) sedation. CONCLUSION Continuous infusion midazolam provides effective sedation in the ICU with few complications overall, especially when the dose is titrated.

Propofol-Nitrous Oxide Versus Thiopental-isoflurane-nitrous Oxide for General Anesthesia

One hundred and twenty patients undergoing elective operations were randomly assigned to receive anesthesia with cither thiopental, 4 mg/kg-isoflurane, 0.2–3%-nitrous oxide, 60–70% (control) or propofol, 2 mg/kg-propofol infusion, 1–20 mg/min-nitrous oxide, 60–70% (propofol). Although anesthetic conditions were similar during the operation, differences were noted in the recovery characteristics. For non-major (superficial) surgical procedures, the times to awakening, responsiveness, orientation, and ambulation were significantly shorter in the propofol group (4 ± 3, 5 ± 4, 6 ± 4, and 104 + 36 min) than in the control group (8 ±7,9 ±7, 11 ±9, and 142 ± 61 min, respectively). In addition, less nausea and vomiting (20 vs. 45%) and significantly less psychomotor impairment was noted in the non-major propofol (vs. control) group. Following major abdominal operations, recovery characteristics did not differ between propofol and control groups. Delayed emergence (>20 min), significant psychometric impairment, and a high overall incidence of postoperative side effects (55–60%) were noted in both drug treatment groups. The authors conclude that propofol-nitrous oxide compares favorably to thiopental-isoflurane-nitrous oxide for maintenance of anesthesia during short outpatient procedures. However, for major abdominal operations, propofol anesthesia docs not appear to offer any clinically significant advantages over a standard inhalational anesthetic technique.

Outpatient Premedication: Use of Midazolam and Opioid Analgesics

The perioperative effects of administering sedative and analgesic drugs prior to outpatient surgery were evaluated. One hundred fifty adult outpatients were randomly assigned to one of six study groups according to a double-blind protocol design. Patients were given placebo (saline) or midazolam (5 mg im) 30-60 min prior to surgery, and then either placebo, oxymorphone (1 mg iv), or fentanyl (100 micrograms iv) 3-5 min prior to a standardized anesthetic technique. Preoperatively, midazolam premedication was associated with a significantly lower anxiety level (37 +/- 29 mm vs. 50 +/- 32 mm, P less than 0.05), higher sedation level (254 +/- 136 mm vs. 145 +/- 109 mm, P less than 0.01), worsening of psychomotor skill (5 +/- 5 vs. 2 +/- 2 dots missed, P less than 0.01; midazolam vs. placebo), and impaired recall abilities. In addition, use of midazolam did not prolong the discharge time. Compared to control patients, those who received fentanyl had a decreased incidence of intraoperative airway difficulties such as coughing (28% vs. 0%, P less than 0.01). Although use of opioids increased the incidence of postoperative nausea (42% vs. 18%, P less than 0.01) and vomiting (23% vs. 2%, P less than 0.01; opioid vs. no opioid), average recovery times were not affected by opioid administration. Oxymorphone use was associated with a lower incidence of pain at home compared with that following fentanyl (46% vs. 74%, P less than 0.05). Finally, preoperative administration of both midazolam and fentanyl or oxymorphone prior to a standardized methohexital-nitrous oxide anesthetic technique did not adversely affect recovery after outpatient surgery.

Pharmacokinetics and pharmacodynamics of alfentanil infusions during general anesthesia

The pharmacokinetic and pharmacodynamic properties of alfentanil were studied in 64 surgical patients. Alfentanil was administered as a loading infusion (25–130 μg/kg) followed by a maintenance infusion (0.25–1.3 μg/kg−1·min−1) as part of a nitrous oxide-narcotic-muscle relaxant technique. Although alfentanil doses of at least 50 μg/kg (in combination with thiopental, 2mg/kg) were required to prevent hemodynamic changes during intubation, apnea or chest wall rigidity frequently occurred with alfentanil loading infusions exceeding 75 μg/kg. The alfentanil clearance rate was significantly lower in patients with liver dysfunction (2.3 ± 1.3 vs 4.2 ± 2.0 ml·kg−1·min1, mean ± SD). In addition, the patients who required opioid antagonists to reverse postoperative respiratory depression had lower clearance rates (1.5 ± 0.7 vs 4.1 ± 1.9 ml·kg−1·min−1) and longer elimination half-life values (406 ± 304 vs 87 ± 53 min). For maintenance of hemodynamic stability during superficial and intraabdominal operations, alfentanil serum concentration-response curves revealed ED95 values exceeding 300 ng/ml and 400 ng/ml, respectively. Our study also demonstrated a wide range of clinical responses to fixed doses of alfentanil. At equivalent doses, some patients required supplemental anesthetics, whereas others required an opioid antagonist. Careful titration of the alfentanil maintenance infusion is recommended to minimize the possibility of postoperative respiratory depression.

Anesthesiologists and perioperative communication

LOOK up communication in a major anesthesiology text, a medical dictionary, or reference book on legal issues and you will not find the word listed, except in the most qualified sense. Yet read these books and you find ample evidence of the importance of communication in anesthesia practice. The word derives from the Latin communicare, meaning to impart, participate. Anesthesiologists, other health professionals, and patients communicate on multiple levels every day. Anesthesiologists participate in activities involving complex social transactions with medical, legal, ethical, and personal significance. They also impart and receive information that affects their participation in other medical professionals’ actions. The quality and quantity of anesthesiologists’ communications has a bearing on the values, outcomes, and standards of their professional work. Recognizing the importance of communication, the American Society of Anesthesiologists has charged the Committee on Communication to “improve public education as it relates to anesthesiology.”‡ Good communication is as important to protecting professional integrity as it is to patient safety and satisfaction. For these reasons, it is as important for anesthesiologists to pay attention to the structure and function of professional communication as it is to learn the pharmacokinetics and pharmacodynamics of drugs.

Design and Implementation of a Perioperative Surgical Home at a Veterans Affairs Hospital

The innovative Perioperative Surgical Home model aims to optimize the outcomes of surgical patients by leveraging the expertise and leadership of physician anesthesiologists, but there is a paucity of practical examples to follow. Veterans Affairs health care, the largest integrated system in the United States, may be the ideal environment in which to explore this model. We present our experience implementing Perioperative Surgical Home at one tertiary care university-affiliated Veterans Affairs hospital. This process involved initiating consistent postoperative patient follow-up beyond the postanesthesia care unit, a focus on improving in-hospital acute pain management, creation of an accessible database to track outcomes, developing new clinical pathways, and recruiting additional staff. Today, our Perioperative Surgical Home facilitates communication between various services involved in the care of surgical patients, monitoring of patient outcomes, and continuous process improvement.

Researching medicine in context: the Arts and Humanities Medical Scholars Program.

In 2000, the Arts and Humanities Medical Scholars Program at Stanford University School of Medicine issued its first grants to medical students interested in researching an area of the medical arts or humanities in depth. To date, 34 projects have been funded, including renewals. The projects encompass a range of genres and topics, from a website on Asian American health and culture to an ethnographic study of women physicians in training in Spain. Two projects are highlighted here: an online history of medicine course and a poetry project. Students are mentored by faculty from a wide array of university departments and centres and submit completion documents to the committee overseeing the programme. Students are encouraged to present their work at conferences, such as the programme’s annual symposium, as well as in publication or other appropriate formats. Future directions include integration with the scholarly concentrations initiative at the medical school.

“It Blew My Mind”Exploring the Difficulties of Anesthesia Informed Consent through Narrative

Exploring the Difficulties of Anesthesia Informed Consent through Narrative THE article by Waisel et al. in this issue of ANESTHESIOLOGY is packed with compelling narratives and evokes both our own experiences and other tales. In one such tale, chronicled in Hold Your Breath—a documentary film by Maren Grainger-Monsen about an elderly Afghani man with advanced stomach cancer—an informed consent misunderstanding results in a heart-rending moment.* Mr. Kochi is filmed during multiple clinic visits with his compassionate, highly skilled oncologist. At each visit we “hear,” through an interpreter, the patient refuse chemotherapy. But it is not until well into the film that we learn the patient misunderstood his treatment options. He had refused chemotherapy because it was offered as a continuous infusion, a method which would interfere with his religious requirements to be “clean” five times a day for prayer. Not until one of his daughters, feisty and completely bilingual, attends an office visit, does it becomes clear to all that he would have consented to any other form of chemotherapy. It is a moment which elicits anger, frustration, and bewilderment on screen. Within, meanwhile, we feel the pang of empathic concern – the pang that reminds us that we are all human in this endeavor called medicine. Anesthesiology, in so many ways, is crystallized medical care. We rarely, if ever, have the luxury of multiple office visits to connect with the patient and family. Hence, if informed consent difficulties occur in the setting of repeated, relatively lengthy visits, how many tribulations must arise in the time-crunch arena where the patient meets an anesthesiologist and must trust (to some degree) this stranger with his or her life? Thus the article by Waisel et al. is welcome indeed. For not only does the study offer us the pangs of acknowledgment of human-human encounters as we read the narratives, but it also brings to the fore the fact that the practice of anesthesiology can be stressful–even without a drop in oxygen saturation or rise in ST segments. In the study, narratives were generated from resident and fellow trainees scheduled to attend an education program on relational and communication skills specifically designed for the anesthesiologist. Trainees were given the following writing prompt: “Write about an informed consent experience with a patient/family that you found particularly challenging.” This is remarkable for several reasons. First, time in the training program was devoted to enhancing a skill set which does not include airway management, drug dosing, regional needle placement, or monitoring technique. Despite early editorial commentary which devalued the use of anesthesia simulators for relational skill development, the recognition and promotion of such skills, attitudes, and knowledge stem in part from the research and educational efforts of those involved in simulation-based anesthesia training. Frequently termed nontechnical skills, teamwork, leadership, and communication skills are embedded and discussed in simulator training and debriefing. In the highly dynamic setting of an operating suite or intensive care unit bay, interpersonal skills are central to good patient care. Second, anesthesia trainees were asked to write. The writing gave residents and fellows a voice in their own training. In being asked to write and using the writings as cases for educational sessions, the teachers were already teaching and conveying key messages to the learners even before any of the sessions began: what you have to say is valuable; what you have to say is unique to you but of interest to others; what you have to say cannot be captured by markings on a multiple choice test; and, perhaps most importantly, there is no single right answer for much of what we do. Interactions between people are complex, multilayered, often ambiguous, and sometimes frustrating. Narrative medicine emerged from the medical humanities field of literature and medicine as an academic discipline that explores the relationships between careful analysis of text and doctoring. The use of writing by doctors and doctors-in-training can be viewed as a tool which promotes reflection; in the setting of a classroom or other group, it promotes community, a deeper presentation of self, and an acknowledgment of vulnerability, fallibility, and other human traits frequently squelched by the press of expectations for perfection in medicine. Third, the study acknowledges a wide, inclusive definition of medical ethics. Rather than left to wander lost and stuporous in a miasma of ethics terminology and systems (autonomy! virtue-ethics! casuistry! deontolThis Editorial View accompanies the following article: Waisel DB, Lamiani G, Sandrock NJ, Pascucci R, Truog RD, Meyer EC: Anesthesiology trainees face ethical, practical, and relational challenges in obtaining informed consent. ANESTHESIOLOGY 2009; 110:480–6.

Medical humanities: demarcations, dilemmas and delights.

Dark/light, question/answer, teacher/student, science/art, female/male. Our lives are chock-a-block with categories. It is human nature to distinguish pattern, indeed it is life-saving on the savannah or on a city street to differentiate movement from stillness. However, we live mostly in the in-between. In the give-and-take between categories, relationship becomes paramount and seemingly definitive boundaries blur. What makes life messy and uncertain also, after all, makes life interesting. Furthermore, anything with a moral quality, such as good and bad, will have associated quandaries and nuances. Medical humanities is an area of scholarship, education and creativity peopled with those who primarily, secondarily or in no way associate themselves with the field. Therein lies the first demarcation, dilemma and delight. From my initial exposure to medical humanities, at a weeklong seminar at Hiram College in the cornfields of Ohio, I knew I was in for an intellectually fascinating ride. In attendance and presenting were theologians, nurses, English professors, social workers, physicians, historians, anthropologists, artists, writers, therapists, educators, ethicists and of course those who wore multiple hats—what a collection of talent and experience! We had (and continue to have) engaging, productive interactions both in the seminar and off-hours. Cross-fertilisation is the delight, professional barriers the dilemma. Language, career development priorities, funding sources and educational domains vary strikingly between groups of professionals. Nonetheless, these people did associate themselves, to varying degrees, with medical humanities. Clearly there are many, many more who work on, write about and wrestle with themes and issues of medical humanities who do not affiliate themselves with the field. For example, few filmmakers, writers …