Year: 2010
Type: article
Study design: Case Report
Abstract: MONITORING of end-tidal carbon dioxide is one of the most important means of determining the physiologic well-being of anesthetized patients. Exhaled carbon dioxide, both in terms of its quantity and pattern, provides detailed information on the cardiopulmonary system. Many things must occur for the exhaled carbon dioxide tracing to appear normal (fig. 1). This hypothetical case acts as a spring board to a discussion of the differential diagnosis of a rapidly rising exhaled carbon dioxide concentration, with special emphasis on malignant hyperthermia (MH).A 55-yr-old man was scheduled to have incision and drainage of a large thigh abscess during general anesthesia. He admitted to extensive substance abuse, including alcohol, tobacco, methamphetamines, and cocaine. He inhaled an unknown quantity of methamphetamines 12 h before his arrival in the operating room. He denied family or personal problems with anesthesia. He did not take any medications. He did not have any history of cardiac or pulmonary disease. He weighed 77 kg and was 189-cm tall. His preoperative blood pressure was 145/85 mmHg, and his resting heart rate was 85 beats/min. His tympanic membrane temperature was 37.8°C. Two hundred milligrams of propofol was administered intravenously followed by 50 mg of rocuronium. The trachea was intubated with an 8.0-mm endotracheal tube. Chest auscultation revealed equal bilateral breath sounds. Mechanical ventilation was initiated with tidal volume = 600 ml and 12 breaths/min. Sevoflurane was started at 2.5% on the vaporizer. Thirty minutes after induction of anesthesia, and 10 min after the surgery had begun, the end-tidal carbon dioxide was 35 mmHg; end-tidal sevoflurane was 2.2%. Over the next 30 min, the end-tidal carbon dioxide increased from 35 to 45 mmHg, accompanied by a slight increase in heart rate from 95 to 105 beats/min. Nasopharyngeal temperature was 38.9°C. The increasing end-tidal carbon dioxide, heart rate, and temperature suggested a physiologic perturbation that required immediate attention and investigation.A thorough check of the anesthesia machine and circuit revealed no leaks. Inspiratory pressures were 15 cm H2O, and chest auscultation demonstrated equal breath sounds with no wheezing; chest excursion with each breath seemed adequate and appropriate for the tidal volume. The ventilation rate was increased to 15 breaths/min. Despite the change in ventilation, the end-tidal carbon dioxide continued to increase to 60 mmHg over 5 min. Heart rate was 110 beats/min.Antibiotics (1 g of cephazolin and 100 mg of gentamicin) were administered in response to surgical manipulation of the abscess and possible bacterial seeding into the bloodstream, but end-tidal carbon dioxide continued to increase and was 65 mmHg despite a further increase in minute ventilation (tidal volume, 900 ml; rate, 20 breaths/min). The electrocardiogram showed sinus tachycardia with normal T waves. There did not seem to be any muscle rigidity, but after placing a urinary catheter to follow urine output, the urine was observed to be dark. A urine dipstick test was positive for hemoglobin or myoglobin. A muscle twitch monitor (electrodes placed over the ulnar nerve) demonstrated only one twitch in a train-of-four stimulation. An arterial blood gas analysis showed pH = 7.13, Paco2= 73 mmHg, Pao2= 225 mmHg, O2saturation = 99%, HCO3−= 19 mEq/l, and K+= 5.0 mEq/l. The end-tidal carbon dioxide was 67 mmHg at the time of the blood gas sampling. The creatine kinase was 1200 IU/l, and the partial thromboplastin time was normal.Carbon dioxide is produced in cells, and after diffusing into the blood, it is transported to the lung for excretion. The differential diagnosis of increased end-tidal carbon dioxide is long but can be separated into two categories: decreased excretion or increased production. The causes of decreased excretion can be further divided into increased inspired carbon dioxide, decreased ventilation, and increased dead space. Increased production can have many causes, as shown in table 1, and is discussed later. Furthermore, there are iatrogenic causes, such as carbon dioxide insufflation during laparoscopy, tourniquet release, and treatment of acidosis with bicarbonate. In addition, the clinician must always consider the possibility of a monitor malfunction, a calibration error, or a gas supply switch.2Whenever there is an unexplained increase in end-tidal carbon dioxide (>10–20% above baseline) and it does not respond to appropriate measures (e.g. , increased ventilation and additional anesthesia), the clinician should consider obtaining an arterial blood gas and electrolyte analysis.Problems with the anesthesia machine can cause increased expired carbon dioxide by increasing inspired carbon dioxide. Exhausted soda lime, channeling through the soda lime, or a faulty inspiratory or expiratory valve might increase the end-tidal carbon dioxide level. Under normal patient conditions, carbon dioxide absorbents will last several hours, but there is substantial variation. Although dye indicators can help determine remaining capacity, these can be inaccurate. Channeling is difficult to detect but could be treated in the same way as in the case of exhausted soda lime, that is, by replacement. A faulty valve in the circle system can be observed and replaced if needed. All these causes would result in increased inspired carbon dioxide, although careful inspection of the waveform is needed. Increased inspired carbon dioxide was not observed on the capnograph of this patient. It is possible that the nadir of the inspired carbon dioxide concentration could be zero, but that some of the inspired gas has carbon dioxide in it, although this would not likely lead to a markedly increased end-tidal carbon dioxide.Inadequate ventilation would also lead to increased carbon dioxide partial pressure. Indeed, high carbon dioxide levels will result whenever metabolic production exceeds excretion. Thus, despite the fact that no changes were made to the ventilator parameters, it is possible that something was amiss with ventilation. There could be a leak in the circle system, such that part of the “tidal volume” is leaking out (e.g. , a nasogastric tube placed inadvertently into the trachea). This leak would be large enough to decrease minute ventilation but small enough to not trigger the low-pressure alarm. Bronchospasm will impede ventilation and is usually associated with wheezing; bronchodilators are often (but not always) effective. Partial tube blockage, either with mucous plugging or a kink, could prevent normal ventilation, and this would lead to increased inspiratory pressures; tube blockage is particularly problematic during pediatric cases where small endotracheal tubes are used. Suctioning the endotracheal tube will remove secretions, but replacement might be needed in extreme cases. Increased dead space would also decrease minute ventilation; causes include adult respiratory distress syndrome.Because there seemed to be no problem with ventilation in this patient, consideration must be given to increased carbon dioxide production as the cause of the hypercapnia. There are numerous causes, and common things occur frequently. Ventilatory problems have already been ruled out. Awakening from anesthesia can increase metabolic production of carbon dioxide; however, the delivery of sevoflurane seemed adequate, and the end-tidal sevoflurane was inconsistent with the scenario of inadequate anesthesia. Furthermore, the patient received rocuronium that would minimize the risk of light anesthesia causing muscle shivering.Sepsis is a common cause of increased metabolism, as is fever from any cause. This patient had pathology (i.e. , an abscess) that could lead to bacteremia, entry of pyrogens into the blood stream, and fever, resulting in increased metabolism and carbon dioxide production. His recent history of substance abuse increases the possibility of toxic drug reaction. For example, methamphetamines or cocaine could cause hypermetabolism (i.e. , metabolic rate above normal) and possibly rhabdomyolysis. Blood toxicology would address this possibility, although results would not be available quickly enough to permit a fast diagnosis.Other possible causes of increased metabolism include surgical stress, seizures, hyperthyroidism, and burns. Although this patient was anesthetized, physiologic responses to surgery (i.e. , surgical stress) will result in increased metabolism. Seizures, especially if there is marked muscle tonic-clonic activity, will markedly increase carbon dioxide production. This patient did not have tonic-clonic seizures. The presence of hyperthyroidism could be investigated with blood tests for thyroid hormone, although this might take considerable time. The diagnosis of burns is self-evident. More rarely, a pheochromocytoma or transfusion reaction might cause an increased metabolic rate.Most of the diseases and situations described in the preceding paragraphs would cause a nonprogressive increased carbon dioxide. MH is looking more likely as the cause of this patient's clinical presentation, in part, because there was a progressive increase in carbon dioxide. Although its occurrence is rare, and there are numerous conditions that mimic it (table 1), the clinician must think of MH, because its treatment is lifesaving and dependent on time of initiation. A clinical grading scale has been developed, which assigns qualitative likelihood to a clinical episode of suspected MH (table 2).3,4In this case, points would be assigned for respiratory and muscle processes, as well as temperature increase and possible cardiac involvement (unexplained tachycardia). The dark urine indicates possible muscle breakdown and is another sign of MH. If rhabdomyolysis is suspected, aggressive therapy is warranted to prevent kidney damage and hyperkalemia. Although increased temperature is part of the syndrome, it usually occurs late and the clinician must not wait for this sign before making the diagnosis and initiating therapy (dantrolene). Delaying diagnosis and treatment will increase mortality.The sevoflurane was discontinued, and anesthesia was maintained with remifentanil and propofol. Dantrolene (2.5 mg/kg) was administered over more than 15 min (the slow rate of mixing and solvation prevents faster administration). Cooling measures were initiated, including placing iced wet towels on the torso. Intravenous fluids were administered at a rapid rate, both to help cool the patient and to prevent renal damage from rhabdomyolysis. There was a rapid resolution of the hypercarbia, and end-tidal carbon dioxide was 25 mmHg; ventilation was decreased (tidal volume, 700 ml; rate, 8 breaths/min). Nasopharyngeal temperature was 37.4°C. After the surgery was completed, the patient was awakened and extubated. Serial blood samples showed no hyperkalemia but creatine kinase peaked at 25,000 IU/L 24 h postoperatively.There are several issues that must be addressed when taking care of a patient who has had a suspected episode of MH. First, the patient must be watched closely for recrudescence. Risk factors for recrudescence include muscular build, a temperature increase, a high score (>35) on the clinical grading scale, and a delayed period between exposure to triggers and the initial reaction.5Frequent monitoring of vital signs, urine, electrolytes, and arterial blood gases should help guide management. Any increases in potassium, worsening acidosis, or resumption of hypermetabolism should prompt repeated doses of dantrolene (1 mg/kg every 6–12 h). Because coagulation can be impaired as a result of the shock state, baseline clotting values (prothrombin time, partial thromboplastin time, and d-dimer) should be obtained. Second, because of muscle breakdown, there is a risk of kidney damage.6This patient should receive alkalinization of his urine and diuretics (furosemide and mannitol) to help clear myoglobin that might have been deposited in the renal tubules. Third, creatine kinase in blood must be determined every 6–8 h until values begin to fall. If markedly increased, the clinician must be more aggressive about administering diuretic therapy to increase renal clearance of myoglobin. In many cases of suspected MH, creatine kinase does not increase or does so only mildly.7Fourth, serum electrolytes need to be monitored, especially potassium, because rhabdomyolysis can lead to hyperkalemia. Failure to diagnose and treat hyperkalemia can lead to cardiac arrhythmias and death. The risk of death for patients with an acute MH episode ranges between 1 and 17%.8,9In unusual cases, MH can present in the immediate postoperative period.10This patient must be advised regarding the presumptive diagnosis of MH and that, because it is almost always an inherited disorder, family members must be told about their risk of having this subclinical disease. Currently, the accepted standard for diagnosis is the in vitro contracture test. Patients with a high likelihood of MH given the clinical events should be actively encouraged to pursue testing as the positive predictive value is increased for them. Genetic testing is also available, but this has limited sensitivity because it does not detect all genetic abnormalities that are likely to be associated with MH.A patient who is suspected of having had a MH episode can be referred to a biopsy center, of which there are 6 in North America (2 in Canada and 4 in the United States), 24 in Europe, and 4 in Australia and New Zealand (updated lists are available).§In general, most biopsy centers will need to review the medical records in addition to speaking with the patient and the anesthesiologist or anesthetist. Once this information is reviewed, a decision is made regarding the advisability of performing the biopsy procedure. Clinical information, along with the biopsy results, can be entered into the MH registries to facilitate future data analysis.The caffeine-halothane contracture test requires fresh muscle sample that must be obtained immediately before testing and therefore in close proximity to the biopsy center. The muscle sample cannot be mailed or sent by express delivery service. The test requires a small muscle sample (2 cm × 2 cm × 2 cm) obtained from the vastus lateralis. A video of the procedure is available for viewing.∥Like all biologic tests, contracture testing has limits on its sensitivity and specificity (the former is the ability to detect the disorder and the latter relates to whether the test will be positive when the disorder is not present). Usually, there is a tradeoff between the two, such that increased sensitivity comes at the expense of decreased specificity. The diagnostic thresholds were established to minimize the possibility of false-negative results. The North American protocol has a sensitivity and a specificity of 97–98% and 78–80%, respectively (although specific values will vary from laboratory to laboratory).11Thus, there is a 2% chance that contracture testing will incorrectly mislabel a MH-susceptible individual as normal, whereas there is a 20% chance that a person without the disease will be labeled as susceptible.Some clinicians question the value of the contracture test other than for research purposes. They argue that, given the less than 100% sensitivity of contracture test, a patient who tests negative still should not receive triggering agents. Thus, if testing will not change anesthetic practice, then why perform invasive and expensive biopsy procedures? Generally, it is quite practical to give anesthesia using nontriggering anesthetics. However, for certain patients (pediatrics, severe asthmatics, and those with difficult airways) and procedures (myringotomy tubes), potent inhaled anesthetics are useful. Further, the implications for family members of patients labeled MH susceptible can become burdensome. If a single patient is incorrectly presumed susceptible without biopsy, what about their children and grandchildren? Biopsy center directors patients procedures were by who were before their MH had been established by cannot a clinician who to give a nontriggering anesthetic to a person who has had contracture testing and who is not susceptible to MH. The however, is that such patients can receive triggering a of occurs in susceptible on exposure to potent anesthetic and or the muscle reaction is by muscle hypermetabolism after exposure to these triggering Patients susceptible to MH in triggering large increases in and metabolism as the muscle to and occurs when the concentration production and levels increase, initiating respiratory and metabolic acidosis, whereas are which to increased rhabdomyolysis will which can lead to acute renal other can and result in should be at the by triggering and administering Dantrolene is a muscle that the of from the the time to it does not at the Once the diagnosis of MH is every should be to and of acidosis with and fluids are important but should be in with dantrolene therapy not in of in is a often inherited as an with and might have an episode on the exposure to triggering whereas another individual might not trigger on repeated There is recent and in including time after exposure to triggering the presence of other anesthetic and to of triggering can the of a MH is to what the clinical genetic is in the that for the The is in muscle where it as a to and Genetic testing for MH in on the There are more than in the have been in on 19 in the for the however, only of susceptible have one of the because of genetic the of does not MH negative between contracture testing and genetic occurs In such cases, patients might have in of the or a in another There be or that have There are only two in North America that perform genetic analysis for problems have the clinical diagnostic value of genetic testing for MH although continued research should its research has on the other have been For example, the that the of the muscle has been to a addition, is a in muscle that, when to in this is present in to be but such a could to MH in patients who not have genetic testing should be for patients with MH through contracture testing to for a If and MH if the is contracture If no are must still muscle biopsy testing to their of creatine kinase can be increased in patients susceptible to MH, although by such an is not diagnostic for this disorder (e.g. , it the other if creatine kinase is increased in an individual who has a who has MH then that individual also be to be of the of MH research has always been the of a diagnostic test. After of the increased sensitivity of muscle of MH-susceptible to or or in vitro muscle contracture testing was as a diagnostic using and drug to the of two the North American MH and the MH their using and in a However, of both showed more or less test and the of the individual to their for the of patients made it difficult to one single protocol for MH in the in vitro muscle contracture testing has been more in several over the it is that the for further MH particularly is in with North clinical in vitro muscle contracture and genetic data of several MH to the of using both contracture testing and genetic to the individual for this is patient because it is that a MH negative diagnosis is The of trigger be in such and in case of a false-negative there are numerous causes of increased end-tidal carbon dioxide, and each can have a it is difficult to the capnograph as a diagnostic by Thus, the diagnostic specificity of is not likely to be It is however, that further research into each cause of increased end-tidal carbon dioxide will of measures as heart rate, blood respiratory and that, when with the will diagnostic a grading scale would be to that for the diagnosis of a MH of the most important of research of MH is to minimize and This could be in several including having a test for MH that is and could be to all patients general anesthesia. Although this might not seem by the of the in it likely that one patients will be for a of diseases and drug and that this could be the however, of all genetic that are associated with and cause MH is Once all are a and specific genetic test can be for MH. will occur and the of genetic will over time. Thus, genetic testing will In addition, are made in a less invasive test than muscle of these in of a small is placed into the and and are through the is in the Patients with MH have increased with normal patients. still and some in the more invasive muscle biopsy procedure. There is also an in testing blood for a diagnosis of MH also not have a thorough of the in the to the clinical syndrome, all the specific regarding the of of Although dantrolene has been it is not a include respiratory muscle with from a with and a replacement for dantrolene would be an still not the between MH and other
Source: Anesthesiology
Institutions: University of Basel, University of California, Davis
Language: English
Subfield: Anesthesiology and Pain Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2030381166