Perioperative Hyperkalemia
Use of inhaled anesthetic agents has been associated with rare increases in serum potassium levels that have resulted in cardiac arrhythmias and death in pediatric patients during the postoperative period. Patients with latent as well as overt neuromuscular disease, particularly Duchenne muscular dystrophy, appear to be most vulnerable. Concomitant use of succinylcholine has been associated with most, but not all, of these cases. These patients also experienced significant elevations in serum creatinine kinase levels and, in some cases, changes in urine consistent with myoglobinuria. Despite the similarity in presentation to malignant hyperthermia, none of these patients exhibited signs or symptoms of muscle rigidity or hypermetabolic state. Early and aggressive intervention to treat the hyperkalemia and resistant arrhythmias is recommended, as is subsequent evaluation for latent neuromuscular disease.
Malignant Hyperthermia
In susceptible individuals, isoflurane anesthesia may trigger a skeletal muscle hypermetabolic state leading to high oxygen demand and the clinical syndrome known as malignant hyperthermia. The syndrome includes nonspecific features such as muscle rigidity, tachycardia, tachypnea, cyanosis, arrhythmias, and unstable blood pressure. (It should also be noted that many of these nonspecific signs may appear with light anesthesia, acute hypoxia, etc.) An increase in overall metabolism may be reflected in an elevated temperature, (which may rise rapidly early or late in the case, but usually is not the first sign of augmented metabolism) and an increased usage of the CO2 absorption system (hot canister). PaO2 and pH may decrease, and hyperkalemia and a base deficit may appear. Treatment includes discontinuance of triggering agents (e.g., isoflurane), administration of intravenous dantrolene sodium, and application of supportive therapy. Such therapy includes vigorous efforts to restore body temperature to normal, respiratory and circulatory support as indicated, and management of electrolyte-fluid-acid-base derangements. (Consult prescribing information for dantrolene sodium intravenous for additional information on patient management). Renal failure may appear later, and urine flow should be sustained if possible.
Since levels of anesthesia may be altered easily and rapidly, only vaporizers producing predictable concentrations should be used. Hypotension and respiratory depression increase as anesthesia is deepened.
Increased blood loss comparable to that seen with halothane has been observed in patients undergoing abortions.
FORANE (isoflurane, USP) markedly increases cerebral blood flow at deeper levels of anesthesia. There may be a transient rise in cerebral spinal fluid pressure, which is fully reversible with hyperventilation.
There is currently no manufacturer warning information available for this drug.
FORANE (isoflurane, USP) may be used for induction and maintenance of general anesthesia. Adequate data have not been developed to establish its application in obstetrical anesthesia.
FORANE (isoflurane, USP), a nonflammable liquid administered by vaporizing, is a general inhalation anesthetic drug. It is 1-chloro-2, 2,2-trifluoroethyl difluoromethyl ether, and its structural formula is:
Some physical constants are:
| Molecular weight | 184.5 | |
| Boiling point at 760 mm Hg | 48.5°C (uncorr.) | |
| Refractive index n20D | 1.2990-1.3005 | |
| Specific gravity 25°/25°C | 1.496 | |
| Vapor pressure in mm Hg** | 20°C | 238 |
| 25°C | 295 | |
| 30°C | 367 | |
| 35°C | 450 | |
| **Equation for vapor pressure calculation: | ||
| log10Pvap= | A + B/T where: | A = 8.056 |
| B = -1664.58 | ||
| T = °C + 273.16 (Kelvin) | ||
Partition coefficients at 37°C
| Water/gas | 0.61 |
| Blood/gas | 1.43 |
| Oil/gas | 90.8 |
Partition coefficients at 25°C – rubber and plastic:
| Conductive rubber/gas | 62.0 |
| Butyl rubber/gas | 75.0 |
| Polyvinyl chloride/gas | 110.0 |
| Polyethylene/gas | ~2.0 |
| Polyurethane/gas | ~1.4 |
| Polyolefin/gas | ~1.1 |
| Butyl acetate/gas | ~2.5 |
| Purity by gas chromatography | >99.9% |
| Lower limit of flammability in oxygen or nitrous oxide at 9 joules/sec. and 23°C | None |
| Lower limit of flammability in oxygen or nitrous oxide at 900 joules/sec. and 23°C |
Greater than useful concentration in anesthesia. |
Isoflurane is a clear, colorless, stable liquid containing no additives or chemical stabilizers. Isoflurane has a mildly pungent, musty, ethereal odor. Samples stored in indirect sunlight in clear, colorless glass for five years, as well as samples directly exposed for 30 hours to a 2 amp, 115 volt, 60 cycle long wave U.V. light were unchanged in composition as determined by gas chromatography. Isoflurane in one normal sodium methoxide-methanol solution, a strong base, for over six months consumed essentially no alkali, indicative of strong base stability. Isoflurane does not decompose in the presence of soda lime (at normal operating temperatures), and does not attack aluminum, tin, brass, iron or copper.