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The induction of general anesthesia often causes a significant drop in blood pressure—an undesirable side effect. A recent publication in our specialty’s leading journal Anesthesiology, “Early Use of Norepinephrine in High-risk Patients Undergoing Major Abdominal Surgery: A Randomized Controlled Trial,” described the use of a prophylactic infusion of the vasopressor norepinephrine to prevent hypotension after the induction of anesthesia. This was a single center randomized trial of 500 patients conducted in France. All patients were having major abdominal surgery, were older than 50 years, and were ASA Physical Status II or greater. Patients were randomly assigned to norepinephrine or ephedrine groups. In the norepinephrine group, a continuous intravenous injection of norepinephrine was started prior to the induction of anesthesia and titrated as needed if hypotension occurred. In the ephedrine group, hypotension was treated with boluses of ephedrine. The incidence of hypotension was significantly lower in the norephedrine group (15%) compared to the ephedrine group (74%); P < 0.001. Medical or surgical complications within 30 days of the surgery occurred in 44% of the norepinephrine group and 58% of the ephedrine group; P = 0.004. The conclusion was that a prophylactic norepinephrine infusion was more effective than repeated ephedrine boluses in preventing postinduction hypotension and may reduce postoperative complications in major abdominal surgery.
Impressive data.
But this data needs to be interpreted in context. Major abdominal surgeries are a small percentage of the 91 million surgeries performed in the United States per year. Major abdominal surgery includes treatment for intraabdominal infections, bowel obstructions, sepsis, malignancy, trauma, and vascular abnormalities. Many patients have significant comorbidities such as cardiac issues, respiratory abnormalities, obesity, infections, shock, or abnormal preoperative vital signs. Many of these patients are at higher risk for hypotension, and consideration of a prophylactic norepinephrine infusion exists for these patients.
Significant post-induction low blood pressure of 76/37 with a low heart rate of 46 beats per minute
Intraoperative hypotension during general anesthesia is a significant problem, linked to a higher risk of postoperative mortality, myocardial infarction, cardiogenic shock, acute renal failure, delirium, and stroke. Hypotension must be treated early to reduce the overall degree of severe hypotension and to preserve end-organ perfusion. Most studies recommend maintaining a minimum mean arterial pressure of 60 – 65 mm Hg, or a systolic blood pressure of 90 mm Hg in non-cardiac surgery.
Preoperative risk factors associated with hypotension include advanced age, low blood pressure before anesthesia induction, hypovolemia, higher American Society of Anesthesiologists (ASA) status, chronic treatment with antihypertensive drugs, and planned high-risk surgery. Patients with a history of hypertension on medication, who are regular users of ACE (angiotensin-converting enzyme) inhibitors or ARBs (angiotensin receptor blockers) or beta blockers, patients who have low pre-induction mean arterial blood pressures, and females are all at increased risk for hypotension following anesthesia induction.
Extrapolating from the Anesthesiology study that prophylactic norepinephrine infusions are widely indicated to prevent hypotension after anesthesia induction is an absurd notion that defies the KISS principle (Keep It Simple Stupid). Transient hypotension after induction in most patients is currently effectively treated with boluses of IV ephedrine, as in the control group in the study. Ephedrine has sympathomimetic β and α effects which promote arterial vasoconstriction and a mild inotropic effect. Ephedrine is usually effective for mild transient intraoperative hypotensive episodes. Norepinephrine is an α1- and β1-adrenergic agonist that can boost or maintain mean arterial pressure and cardiac output. Norepinephrine infusions are commonly utilized in intensive care units, during cardiac surgery, and for anesthetics in critically ill patients. Preparing a norepinephrine infusion, and preparing an infusion pump to administer the infusion safely, are efforts simply not necessary for most ASA II patients for most surgeries. Most surgical patients will not require a prophylactic norepinephrine infusion to treat post-induction hypotension. The costs of a prophylactic norepinephrine infusion are high, e.g. $495 for one infusion bag, plus the price of the IV tubing and the infusion pump.
Infusion pump used for norepinephrine
Risks of iatrogenic complications are from norepinephrine are real and include inadvertent bolus administration or overdose of this potent catecholamine, which can cause extreme hypertension.
The doses of anesthesia induction drugs matter. In the Methods section for the Anesthesiology study, the anesthetic inductions were described as a combination of a hypnotic drug (etomidate or propofol), an opioid drug (sufentanil), and a paralyzing drug (cisatracrium, atracurium, or rocuronium). The choices of the drugs, and the doses of the drugs, were not controlled in the study. This is a significant issue, because the doses of the hypnotic drugs and the doses of the narcotics have a great influence on the degree of hypotension that can result. Cardiac output (CO) and systemic vascular resistance (SVR) are determinants of the mean arterial blood pressure (MAP). Most anesthesia drugs, including hypnotics and narcotics, can alter either the vascular tone or the cardiac output. The higher the dose of these drugs, the more effect they have on decreasing the blood pressure.
Induction doses are typically based on a patient’s age and weight. Elderly, sick, or frail patients require lower doses of both the hypnotic drug and the narcotic. A relative overdose of hypnotic and/or narcotic is the most common iatrogenic cause of post-induction hypotension. A 25-year-old, 70-kilogram athletic male may tolerate IV induction with 2 mg of midazolam, 100 mcg of fentanyl, and 200 mg of propofol for a laparoscopic appendectomy, but those same doses would cause significant hypotension if administered to an 80-year-old, 50-kilogram female for the same surgery. Experienced anesthesiologists are aware of this.
I’ve observed that less experienced anesthesia professionals often overdose older, smaller, or more frail patients by ignorance of this principle, causing iatrogenic hypotension. In my residency training I was taught to routinely administer 250 mcg of fentanyl prior to anesthetic induction with propofol or sodium pentothal, to “blunt the hypertensive response to laryngoscopy and endotracheal intubation.” But following the transient stressors of laryngoscopy and endotracheal intubation, what occurs is typically thirty minutes of positioning, prepping, and draping of the patient, during which there is no surgical stimulation, and blood pressure predictably sags. What results is hypotension with MAPs less than 60 mm Hg, which requires doses of ephedrine to maintain adequate blood pressure while everyone is waiting for the onset of the scalpel and surgical stimulation.
What I currently teach is to limit the preintubation fentanyl dose to 50 mcg for most patients, followed by propofol induction. With lower narcotic dosing, the incidence of post-induction hypotension is minimal. I realize this is not research data, but my attestation is that less than 5% of these patients require ephedrine or any treatment for post-induction hypotension.
Dosages matter. Dosages were not controlled in the Anesthesiology study.
The question going forward is “which patients should have a prophylactic norepinephrine infusion?” Further research will be necessary to define the indications. Sixty-four million outpatient surgeries are performed each year—70% of the total surgeries in America—and none of these cases should require a prophylactic norepinephrine infusion. Ambulatory surgery requires screening to eliminate patients with significant medical comorbidity, and screening to eliminate risky surgical procedures. As the Medical Director of a busy multispecialty ambulatory surgery center, I have no intention of enabling the practice of routine prophylactic norepinephrine infusions at a freestanding outpatient surgery center.
Simply put, a small minority of cases may benefit from a prophylactic norepinephrine infusion, but an overwhelming majority of anesthetics should never adopt the results of this study. Will this norepinephrine study in Anesthesiologychange the way anesthesia is practiced? Will anesthesiologists cue up a norepinephrine infusion prior to induction for a patient having a laparoscopic cholecystectomy? I doubt it. Will patients expect to have a norepinephrine infusion prior to induction for their outpatient rotator cuff repair? No. Future studies will better define which patients—likely ASA III patients having major abdominal, thoracic, or emergency surgery—are candidates for a prophylactic norepinephrine infusion prior to anesthesia induction. Until then, keep your anesthetics simple, keep your induction doses lower for frail or small patients, use ephedrine for the majority of mild perioperative hypotension episodes, and don’t order hundreds of dollars of prophylactic norepinephrine infusions/norepinephrine infusion pumps to treat most patients.
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