Medical brain notes 7

  The liver We expect this large organ to do its biotransformation magic on many of the drugs we give. For example, the liver avidly removes propofol, which is said to have a hepatic extraction ratio (HER) of close to 1. Reduced liver blood flow will, there-fore, reduce the rate of propofol biotransformation. The rate of biotransformation of drugs with a low HER, such as thiopental, will be less affected by changes in liver blood flow. Remember that the liver normally receives about 25% of cardiac out-put, roughly 2/3 of that via the low-pressure portal system, the rest by way of the hepatic artery delivering oxygenated blood. General anesthesia tends to reduce cardiac output and, proportionally, hepatic arterial blood flow more than portal blood flow. The hepatic circulation is also richly supplied with alpha recep-tors; hence the administration of alpha active vasopressors will reduce hepatic    blood flow. Because of the enormous reserves of the liver, we rarely see th...

  The kidneys The kidneys concern us when drugs or their products of biotransformation need to be eliminated in urine. For this route out of the body, the substances need to be non-protein-bound so that they make it through the glomeruli and are then ionized so as to escape tubular reabsorption.   Impaired renal function becomes relevant with advancing years (creatinine clearance declines with age), with low cardiac output and decreased glomerular filtration, and with renal disease. The elimination of some drugs can be affected by decreased renal function. Of greatest interest to the anesthesiologist are a number of muscle relaxants such as pancuronium and doxacurium and their antagon-ist, neostigmine. Thus for patients in renal failure, we might elect atracurium or cisatracurium, muscle relaxants that undergo hydrolysis in plasma making them independent of renal excretion. Patients in renal failure present special challenges not only because they cannot eliminate drugs in uri...

  The blood Three functions of the blood demand attention: its volume, its oxygen-carrying capacity, and its ability or propensity to clot. Volume Blood volume varies with age, weight, and sex (see Vascular access and fluid management). As we know from donating blood, the average adult can easily lose 500 mL without conspicuous consequences. Indeed, healthy patients can tolerate a blood loss of 20% of their total blood volume. The body compensates for such loss by mobilizing interstitial and eventually even intracellular water to replenish the decreased intravascular volume. In the process, the hematocrit will fall gradually over a couple of days. Oxygen-carrying capacity With a loss of blood volume, the patient also loses oxygen carrying capacity. Compensatory increases in cardiac output can insure uninterrupted delivery of oxygen, even in the anemic patient. As hematocrit decreases to about 30%, fluidity of blood increases, which improves flow and thus aids in the delivery of a h...

  The basic approach Many different approaches to general anesthesia are possible. Often, pre-operative preparation includes the administration of drugs to (i) minimize the chance of aspiration of gastric juice, (ii) minimize anxiety and – if necessary –  provide analgesia. Once the patient is in the operating room, we aim to deni-trogenate the patient’s lungs, followed by induction of anesthesia. One technique is to induce sleep with thiopental, give a paralyzing dose of succinylcholine to facilitate intubation of the trachea, and then maintain anesthesia with a halo-genated anesthetic vapor administered together with nitrous oxide and, of course, oxygen. Muscle relaxation during the operation might be accomplished with one of the non-depolarizing neuromuscular blockers, frequently called “muscle relax-ants.” Another technique might start with propofol instead of thiopental and it might rely on large doses of an opiate, such as fentanyl and, to assure amne-sia, a low concentr...

Theories of anesthesia Please note that we are speaking of theories (in the plural!). This simply reflects the fact that a single theory could not possibly explain the phenomenon of induced coma: there are simply too many different substances that can render a person reversibly unconscious. In some instances, we can imagine a mecha-nism, for example, lack of oxygen will stop the functioning of cells dependent on oxygen. But then think of a knock on the head, very high or low blood sugar, alcohol, sleeping pills, noble gases (xenon), inorganic gases (nitrous oxide), ace-tone, organic solvents such as chloroform, carbon tetrachloride, trichlorethy-lene, ethylene, diethyl ether, and a slew of halogenated compounds, not to mention narcotics, benzodiazepines, barbiturates, steroids, phenols, etc. To complicate matters, one fluorinated hydrocarbon, hexafluorodiethyl ether, is a convulsant (in the past used instead of electroconvulsant therapy in the treatment of depression) while several of ...

  Reduce the risk of aspiration (Table  12.1 ) The aspiration of acid gastric juice can lead to a nasty chemical burn of the trachea and bronchi and to bronchospasm and pneumonitis and, potentially, to death. We aim to reduce gastric volume and limit acidity. Gastric juice with a pH of 2.5 or less is thought to cause dangerous chemical burns when aspirated. We have several methods to reduce the hazards of aspiration of acidic juice: ·             Buffer the gastric acid with an antacid. Many different agents are available. We prefer a non-particulate liquid, which not only mixes more readily in the stomach but also causes less harm when aspirated than would be true for a particulate antacid. Sodium citrate (trisodium citrate) or Bicitra® (sodium citrate and citric acid) – which are liquid – find common use in anesthe-sia. We give 15–30 mL by mouth within 30 minutes before induction of anesthesia. ·     ...

  Barbiturates The drugs with the longest history of intravenous use in anesthesia are the barbiturates. While many different barbiturates have been synthesized and used, the drugs most commonly found in current anesthesia practice are thiopental (Pen-tothal®) and methohexital (Brevital®). These drugs share the basic barbituric acid foundation (Fig.  12.1 ), which by itself has no CNS depressant effect. Sub-stitutions on position 5 give us pentobarbital, a slow- and long-acting hypnotic. Simply substituting sulfur for the oxygen on position 2 turns the drug into the highly lipid soluble, fast-acting thiopental. After an intravenous thiopental bolus, e.g., 4 mg/kg, the patient falls asleep in less than a minute and comes around again within a few more minutes. The drug  owes its rapid onset of effect to the S= substitution on position 2 and to the fact that the “vessel rich group” (tissues with a high blood flow; especially the brain) gets the first lion’s share of the dru...

  Inhalation anesthetics (Table  12.5 ) Before discussing the agents one by one, we need to deal with the question of the uptake and distribution of inhaled drugs. Uptake and distribution of inhaled anesthetics   Behind this bland title lurks a concept that has baffled students for years, yet it is fairly straightforward. Here are the facts:   (i)         Solubility of the anesthetic in blood has nothing to do with its potency. Indeed, anesthetic effectiveness has to do with the partial pressure of the drug and not with the amount of drug in solution.   (ii)      Anesthetics taken up by the blood flowing through the lungs are distributed into different body compartments, depending on the blood flow these com-partments receive, the volume of the compartment, and the solubility of the anesthetic agent in that compartment.   (iii)    The partial pressure exerted by a vapor in solution has nothing...