Barbiturate Overdose and Hypoventilation - Coursework Example

Barbiturate Overdose and Hypoventilation 07 May Barbiturate Overdose and Hypoventilation Introduction Drug abuse, including barbiturate overdose, remains one of the major social and medical problems. The development of new drugs increases the risks of improper use and unintended consequences, whereas clinical manifestations of drug overdoses and their management turn into a serious diagnostic challenge. Despite recent advances in medicine and toxicology, the issues and risks of barbiturate intoxication continue to persist. Because barbiturates are associated with increased lethal risks, they often become a convenient instrument of realizing suicidal intentions among youths and adults. For individuals who ingest abnormal levels of barbiturates, the risks of hypoventilation and respiratory failure are the highest. CNS disorders associated with the use of barbiturates and the failing efficiency of the thoracic bellows can readily become the main causes of hypoventilation. The use of respiratory stimulants in respiratory problems remains an object of acute debates. In all instances of barbiturate poisoning, prompt intubation and analeptic drugs are required, to reduce the scope of hypoventilation and respiratory acidosis that facilitate the passage of barbiturate substances across the blood. Mechanisms of action Despite the recent advances in medicine, barbiturates remain a common instrument of medical treatment. Barbiturates may not be commonly available to patients, but the risks of barbiturate overdose are always high. Barbiturates exemplify a large class of structurally related chemical compounds that depress the activity of nervous tissues and muscles (Yadav 58). They have the potential to cause a wide range of effects on the Central Nervous System (CNS), from mild sedation, to coma and even death (Yadav 58). The depth and severity of the effects directly depends on the amount of barbiturates ingested by individuals. The mechanism of barbiturate action on the human organism is rather straightforward. “Barbiturates act at gamma-aminobutyric acid-A receptors” (Johnson 318). The latter is a complex transmembrane protein complex made of five subunits, each having multiple points of binding to gamma-aminobutyric acid-A receptors (Johnson 318). Barbiturates represent a unique medium of influences on the actions of gamma-aminobutyric acids (Johnson 318). In large quantities, barbiturates can activate CI-channels even despite the absence of gamma-aminobutyric acid (Johnson 318). The mechanism of barbiturate overdose on respiration can be understood in the following way: depending on the dose, barbiturates result in the reduction of respiration, with extreme doses leading to respiratory arrest (Doweiko 70). This is mainly because barbiturates reduce the sensitivity of the medulla oblongata respiratory centers to the rising levels of carbon dioxide (Doweiko 70). Similar processes result in hypothermia, which is not uncommon in barbiturate intoxication. When barbiturates are ingested at above-normal levels, they usually lead to tachycardia, the loss of reflex activity and hypotension (Doweiko 71). Changes in respiratory activity under the influence of above-normal levels of barbiturates are directly related to their toxicology. The fact is that barbiturates directly influence the central nervous system which, when its activity under the effects of barbiturates reduces, leads to the subsequent decrease in ventilation (Johnson 318). Barbiturates are responsible for changes in both respiratory drive and rhythmic characteristics (Johnson 318). In huge doses, barbiturates can readily result in the elimination of respiration (Johnson 318). This is why acute barbiturate overdoses often become fatal. Other drugs can further exacerbate the depressed-respiratory effects of barbiturates: sublethal doses barbiturates further combined with benzodiazepines and ethanol can cause life-threatening ventilation complexities (Johnson 318). It should be noted, that ventilation by itself is the process of gas movement into and out of the lung, and normal ventilation usually involves a complex interplay of CNS-regulated respiratory centers, peripheral nerves and musculoskeletal systems (Murtaugh 33). Once any of these systems is impaired, hypoventilation may follow. The most common causes of hypoventilation include CNS impairments following barbiturate overdoses and intoxications of different nature, neoplasia and cerebral trauma, peripheral nervous system problems, as well as the use of drugs that block neuromuscular functions (Murtaugh 33). In patients receiving mechanical ventilation, iatrogenic hypoventilation risks should not be overlooked (Murtaugh 33). All this information can become a useful guide in the management of patients facing barbiturate intoxication. Causes As previously mentioned, depressed CNS function under the influence of above-normal doses of barbiturates is the most common cause of hypoventilation. Overdoses involving barbiturates and methadone often lead to pulmonary edema (Saba et al. 735). The five most common etiologies of hypoventilation and pulmonary edema in barbiturate overdose include: (a) severe hypoxia; (b) an increase in the capillary permeability following the direct toxic effects of barbiturates on the pulmonary capillaries; (c) myocardial stress caused by the direct toxic effects of barbiturates themselves or severe hypoxia; (d) allergic reactions to the drug, and (e) hypersensitivity to the toxic contaminant (Saba et al. 735). All these factors can be equally responsible for the development of hypoventilation in the cases of barbiturate overdose. Saba et al. write that chemical poisons similar to barbiturates greatly affect the capillary permeability of lungs. This, in turn, causes an increase in proteins in the edema fluid, further affecting the stability of the alveolar-capillary membrane (Saba et al. 735). However, these characteristics and processes are not unique for barbiturate overdoses, and can be also found in other health conditions, for example, in cardiac failures. Moreover, to a large extent, in patients who experience barbiturate intoxication, the risks of heart failure and myocardial ischemia dramatically increase. As a result, they can be considered as the most likely explanation to hypoventilation in barbiturate overdose cases (Saba et al. 735). The direct toxic effects of barbiturates and cardiovascular complications of barbiturate overdoses, as well as hypersensitivity of patients to barbiturate doses can be equally responsible for the development of hypoventilation symptoms. Individual responses to various doses of barbiturates vary considerably across individuals and depend on numerous factors (Saba et al. 735). For example, for patients who have recently abstained from drugs, even small doses of barbiturates can cause unpredictable health consequences. When combined with other agents and contaminants, barbiturate overdoses create an enormous task of isolating the most active agent responsible for hypoventilation (Saba et al. 735). In extreme doses of barbiturates, the human organism may be deprived of a capacity to engage effective compensatory mechanisms and maintain an effective operation of lungs (Saba et al. 737). Simultaneously, pulmonary edema in barbiturate overdose patients is less likely, even if the degree of hypoventilation is equal or more serious than that of a narcotic overdose patient (Saba et al. 737). “The organs involved in the barbiturate overdoses have a relatively longer period of time to adjust to the initial but gradual insult due to the oral route of administration” (Saba et al. 737). The fact that barbiturates cannot be administered through injections greatly reduces the risks of pulmonary failure in barbiturate overdose patients. More often than not, pulmonary edema in barbiturate overdose patients is the result of an overzealous attempt to diurese these patients, leading to volume overloads (Saba et al. 737). It should be noted, that there are situations when patients can develop hypoventilation even when their lungs are normal. In these situations, the primary cause of hypoventilation can be the reduced efficiency of the thoracic bellows (Lassen 891). There is a certain level of tidal volume that has to be maintained and which, when reduced to an abnormal level, quickly leads to hypoventilation (Lassen 891). This is actually an alveolar-induced type of hypoventilation, which does not manifest through a serious respiratory distress but can impede patient’s ability to compensate for the emerging ventilation deficiency. In this type of hypoventilation, the levels of gases are still normal but biochemical hypoventilation continues to persist (Lassen 891). Its symptoms are varied and depend on the speed with which it develops: the faster hypoventilation the more severe its symptoms become. In these situations, experiencing an air hunger is the most common patient complaint, whereas many patients may also be sweating, apprehensive, cyanosed and restless, as well as confused (Lassen 891). In the first stages of hypoventilation, the blood pressure may rise, leading to a capillary shock (Lassen 891). Most patients in this state are conscious and mentally clear, with their coughing and swallowing reflexes preserved (Lassen 891). This, however, does not mean that these patients do not require objective evaluation of their health state. Risks The recent developments of medicine have substantially reduced the risks of fatal outcomes in barbiturate overdoses. However, the risks of pulmonary complications are abundant and usually manifest once the doses exceed 83 mcg/kg/min (Lafferty). These are the doses that are relevant for adults older than 18 years (Lafferty). The risks and doses for younger patients are not provided. There is also no information about the rates and doses of barbiturates that make the risks of hypoventilation the likeliest. More often than not, hypoventilation is assumed to be a common element of barbiturate overdosing, once the rates of ingestion exceed 83 mcg/kg/min (Lafferty). Adaptation/ compensation Due to the complexity of hypoventilation in barbiturate overdose patients, the process of adaptation and compensation usually involves two stages. First is an acute compensatory response that occurs 10-15 minutes after the initial onset of hypoventilation and the rise of PCO2 (Murtaugh 33). At this stage of adaptation/ compensation, phosphate, hemoglobin or lactate will serve an effective intracellular buffer, leading to the creation of HCO3 that is returned to the plasma (Murtaugh 33). This process of adaptation and response to hypoventilation is not as strong as at the second stage of adaptation. The second stage of adaptation is called chronic compensatory response and usually takes between 2 and 5 days to become fully effective. In this period, not only lungs but kidneys, too, adapt to changes in the acidic environment through acid excretion (Murtaugh 33). At the second stage of adaptation, the risks of chronic respiratory acidosis also decrease (Murtaugh 33). This is also the time required for the full recovery of the respiratory system in the cases of barbiturate overdose. Treatment There is still no agreement as to whether or not respiratory stimulants should be used to alleviate hypoventilation in barbiturate overdose cases. Managing patients with barbiturate intoxication and respiratory problems usually involves more than one drug and a variety of procedures, which are intended to reverse possible pathophysiologic alterations in barbiturate overdose patients (Bickerman & Chusid 53). However, it is clear that cardiorespiratory support should be provided the moment barbiturate overdose is detected and confirmed. The process of treatment begins by clearing patients’ airways and inserting of oral airway (Kiran, Chhabra & Nandini 481). Hypoventilation is one of the first health complications to be addressed in barbiturate overdose patients, since it facilitates the passage of barbiturates across the blood system into the CNS (Kiran et al. 481). Then follows fluid therapy aimed to correct the fluid balance and maintain a reasonable level of electrolytes; the latter will help to eliminate the signs of hypotension (Kiran et al. 481). In order to eliminate the symptoms or risks of hypoventilation, measures to prevent absorption and remove barbiturates should be taken. The former involves gastric lavage, if not more than 2-4 hours have passed since the moment of ingestion, or activated charcoal administered through nasogastric tube (Kiran et al. 481). To remove barbiturates from the human organism and avoid further risks of hypoventilation, frequent doses of activated charcoal, forced dieresis, and hemodialysis are used to alleviate the symptoms of barbiturate intoxication. A one-session six-hour hemodialysis can remove as many barbiturates as are usually removed during a 24-hour session of sustained dieresis (Kiran et al. 481). Analeptic drugs and supportive care are to provided at later stages of the treatment process. All discussed measures have the potential to either eliminate or prevent the risks of hypoventilation in patients experiencing barbiturate overdose/ intoxication. Summary Barbiturates are commonly available to individuals in the form of various medical preparations. The mechanism of barbiturates’ effects on the respiratory function is rather simple and understandable. Depending on the dose, barbiturates result in the reduction of respiration, with extreme doses leading to respiratory arrest. Barbiturates directly influence the central nervous system which, when its activity under the effects of barbiturates reduces, leads to the subsequent decrease in ventilation. The causes of hypoventilation in barbiturate overdose patients can vary. More often than not, changes in CNS and cardiovascular function lead to the subsequent impairments in the respiratory system. In patients with normal lungs, the reduced efficiency of the thoracic bellows is the most common cause of hypoventilation. Patients with barbiturate doses exceeding 83 mcg/kg/min are at the highest risks of hypoventilation. Adaptation/ compensation involves two main stages, and the process of treatment should involve cardiorespiratory support and measures intended to prevent absorption and eliminate barbiturates from the organism. Works Cited Bickerman, Hylan A. & E. Leslie Chusid. “The Case Against the Use of Respiratory Stimulants.” Chest, 58 (1970): 53-56. Print. Doweiko, Harold E. Concepts of Chemical Dependency. Cengage Learning, 2011. Print. Johnson, Bankole A. Addiction Medicine: Science and Practice. Springer, 2010. Print. Kiran, Shashi, B. Chhabra & D. Nandini. “Management of Barbiturate Poisoning – A Case Report.” Indian Journal of Anesthesia, 46.6 (2002): 480-482. Print. Lafferty, Keith. “Barbiturate Toxicity.” Medscape, 2010. Web. 07 May 2012. Lassen, H.C. “Hypoventilation in Patients with Normal Lungs, Poliomyelitis, Myasthenia Gravis, Barbiturate Poisoning, Etc.” Annals of the New York Academy of Sciences, 121 (1965): 891-897. Print. Murtaugh, Robert J. Critical Care. Teton NewMedia, 2002. Print. Saba, George P., James Everette, Burton A. Johnson, Frederick P. Stitick & Barry Burns. “Pulmonary Complications of Narcotic Abuse.” Environmental Medicine, 122.4 (1970): 733-739. Print. Yadav, A.V. Pharmacology & Toxicology. Pragati Books, 2008. Print. Read More