Organophosphate is an assorted group of organic and synthetic agents commonly used in the agricultural industry. Organophosphates are broken down into different classes which include insecticides, herbicides and nerve gases which all differ either with the selectivity and potency due to its chemical structure. Over past decades, the development of manmade organophosphates has impacted the environment which has resulted in health implications such as toxicity for humans and animals. Organophosphate's effectiveness is highly used to protect crops from insects, although due to its non-selective toxicity for the nervous system, it is considered deadly for humans. The use of organophosphate has proven to be highly efficient for the quality of crops, although misuse has resulted in tremendous consequences to society as it has been used for chemical warfare agents, suicides and also accidental exposure can lead to many health issues.
Acetylcholine is a neurotransmitter that is affected by organophosphate pesticides and plays an important role as a neurotransmitter within the autonomic and central nervous system as it is responsible primarily for inhibitory and excitatory effects on effectors organs, communication between neurons in the autonomic ganglia and innervations of skeletal muscle at the neuromuscular junction. Acetylcholinesterase is an enzyme which is responsible for maintaining the homeostatic balance of acetylcholine. Homeostatic balance of acetylcholine is regulated through the breakdown on acetylcholine into its basic fundamental elements, choline and acetate. The main mechanism of organophosphate is that is disables the breakdown of Acetylcholinesterase on nerve terminals (Albuquerque et al., 2006). Acetylcholinesterase inactivation results in amassing of Acetylcholine within the nervous system, abundantly affecting the cholinergic synapses. Muscarinic and nicotinic receptors thereby become over stimulated causing cholinergic toxicity. On the contrary, when there are increased levels of acetylcholine within the synaptic cleft this results in the nicotinic receptors becoming over stimulated, which consequently results in unexpected muscle contractions and twitching eventually leading to paralysis. When the muscarinic receptors become over stimulated this causes an increased amount of parasympathetic mediated effects which is typically seen as the cholinergic syndrome 'SLUD' (Salivation, Lacrimation, Urination, and Defecation) (Kamanyire & Karalliedde, 2004).
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Patients who suffer organophosphate poisoning are often categorized into three stages of toxicity, which are all dependent on the duration of initial exposure. Within the first 24-72 hours after organophosphate exposure, patients will develop into the condition of acute cholinergic crisis (Singh & Khurana, 2009). This results in an overload stimulation of post-synaptic neurons causing 'SLUD' which is characteristics of cholinergic symptoms. 24-96 hours after the initial acute phase, patients will also suffer abnormal twitches which progresses into intermediate syndrome as there is a constant depolarization at the nicotinic receptor site. After the resolution of cholinergic crisis, the commencement of intermediate syndrome occurs and only presents symptoms which are seen in nicotinic toxicity. (Badhe & Sudhakar, 2006). Patients in this phase pose great development of respiratory failure where the diaphragm and other muscles of respiration is paralysed, as it is evident that the clinical feature of intermediate syndrome consist of muscle paralysis and weakening of respiratory muscles (Jayawardane, Senanayake & Dawson, 2009).Patients with intermediate syndrome are often in an altered conscious state and are not capable of clearing the accumulation of excess mucus within their own airway and will also struggle to breathe due to the respiratory muscles being paralyzed. Therefore, when caring for patients with these symptoms, Paramedics must provide adequate, efficient and effective ventilatory care in order for patient to survive. The final stage is known as organophosphate induced delayed polyneuropathy and it is when patients relapse which occurs 7-21 days after initial exposure. Patients usually show signs and symptoms of muscle weakness and often pins and needles in the hands and feet along with other sensory dysfunctions (Jokaovic, Kosanovic, Brkic & Vukomanovic, 2011).
Route of exposure:
Organophosphate's are one of the most common causes of poisoning worldwide and is the most common form of poisoning on workers within the agricultural field because they are continuously exposed to insecticides through their line of work, constantly dealing with poisonous products and environmental areas where there is a lot of exposure to air borne pollutants. Toxicity to Organophosphates to humans is effective through the different routes of entry in which organophosphate particles can enter the body. Many agricultural workers are commonly accidently poisoned because they come into contact with contaminated materials as toxicity can occur through inhalation, absorption through the dermal, and often through ingestion of foods that have been previously treated with insecticides or herbicides (Pandit et al., 2011). Due to its chemical structure, organophosphates are lipid soluble. Being highly lipid soluble they are easily absorbed through the body which crossed the blood brain barrier to cause effects on the nervous system (Kamel et al., 2005).
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To determine whether a patient has been exposed to organophosphates, paramedics need to assess the patient and look for distinct signs and symptoms of organophosphate toxicity. The only assessment for diagnosing organophosphate toxicities in a patient is through analysis of a blood sample where they measure red blood cell Acetylcholinesterase. Depressed numbers of red blood cell Acetylcholinesterase levels are a studied to show biochemical indication of excessive organophosphate absorption in the body (Albuquerque et al, 2006)
Paramedics who suspect a patient to have organophosphate poisoning should take immediate action to protect them from being contaminated. This can be prevented with personal protective equipment where gloves, goggles, face masks and gowns should be worn as a preventative measure. Without this personal protective equipment, paramedics are open for exposure to organophosphates as it may be transferrable via air born particles or direct skin contact to contaminated clothing items. Other preventative actions need to occur such as placing the patient in a Quarantined and controlled environment, and patients need to be washed down thoroughly to prevent any further contamination through skin (Roberts & Aaron, 2007). Paramedic's response time to patients with organophosphate poisoning is crucial as they require oxygen therapy and administration of anticholinergic drugs such as atropine. Before intubating the patient with an endotracheal tube, paramedics need to ensure that the patient's airway is clear from any obstructions, otherwise adequate and effective ventilation may be compromised. Airway management is vital in the survival of the patient as the patient will be in an altered conscious state, where they require mechanical ventilations by the paramedics due to respiratory muscles being paralyzed. Patients have often developed respiratory arrests during the acute and intermediate phases therefore additional monitoring of the respiratory is necessary. Once the paramedics have successfully secured the airway, administration of atropine intravenously is required to decrease the effects of cholinergic symptoms (Eddleston, Buckley, Eyer & Dawson, 2008). Initial administration dose of Atropine Sulphate is 1200mcg IV and subsequent doses of 1200mcg IV every 5 minutes (Clinical Practice Guideline: For Ambulance and MICA Paramedics, 2012) until cholinergic symptoms subside. Immediate transportation of the patient to the intensive care unit plays an important role in whether the patient can make a full recovery.
Mechanism of action:
Within Ambulance Victoria, Atropine is currently the only anticholinergic drug used. Atropine is a competitive antagonist at muscarinic receptors and in the pre hospital setting, administration of IV atropine is very successful in blocking the effects of cholinergic symptoms that are caused by organophosphates (Albuquerque et al., 2006). Antagonism of the muscarinic receptors on glands and smooth muscles allows for enhancements of ventilation due to relaxation and bronchial dilation. There are no contraindications for atropine for the use of a patient in an altered conscious state, but pre causes need to be considered as high dosages can cause cardiac problems due to the sympathetic reactions caused by atropine. The effective use of Atropine is limited against nicotinic symptoms as it is ineffective in reversing muscle weakness, paralysis and respiratory depression (Eddleston et al., 2006).
New drugs are constantly being trialed and formulated to further advance the treatment for organophosphate intoxication. Atropine is limited on the nicotinic receptor so to overcome these issues development of a new drug, oximes, has been created as oximes target the reactivation of Acetylcholinesterase. Pralidoxime is a recently developed oximes that is also able to reactivate organophosphate inhibited by Acetylcholinesterase by attaching to the site where cholinesterase inhibitor has attached, then attaches to the inhibitor, which then removing the organophosphate from cholinesterase, which therefore reducing levels of acetylcholine back to equilibrium (Whetherwall, Prince, Mumford, Armstrong & Scott, 2007). Unlike atropine, which has been clinically proven to be an effective antidote for organophosphate poisoning, which has been approved for human uses, Pralidoxime still remains a controversy with concerns on whether it actually improves patient's outcomes. Studies have extensively analyzed the clinical effectiveness if oximes, especially the optimum therapeutic dosages treatment, as it has come under much scrutiny (Bairy, Vidyasagar, Sharma & Sammand, 2007). Furthermore there have also been many clinical trials conducted that show oximes may improve patient outcome if it is administered early in addition with administration to atropine in patients whom suffer moderate to server organophosphate poisoning cases(Bairy et al., 2007)
Paramedic Clinical Relevance:
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Although we know organophosphate to be highly toxic to humans, there currently are no laws or regulations that govern the sale of these toxic chemicals. The drug schedule states that organophosphates are listed under very dangerous poisons but are not classed as a controlled drug, thus these chemicals can easily be obtained. Recent studies have showed that there has been a rise in accidents and intoxication with main concerns in developed countries due to the relative ease of which these chemicals can be obtained over the counter (London, Fisher, Wesseling, Mergler & Kromhout, 2005). Deaths relating to organophosphate poisoning is on the rise, and this poses a great issue concerning paramedics as their pre hospital management of organophosphate poisoning is essential in the survival of the patients, as majority of mortalities are caused by serve respiratory depression, and a delay in administration of antidotes and adequate ventilatory support is vital in patient outcome. Expansions of new drugs such as Pralidoxime have been proven to be effective in treating organophosphate poisoning by decreasing levels of Acetylcholine binding to the muscarinic receptor. This drug is only used in emergency department in addition with atropine and has not yet been introduced to Ambulance Victoria due to lack of proven studies that this drug has an effective effect in the pre hospital setting, although with further clinical tests and studies, the use of Pralidoxime may in due course make its way into the Ambulance Victoria Clinical Practical Guidelines.
Paramedics play a significant role in organophosphate poisoning as the outcome of the patient relies heavily in the hands of paramedics. This essay discusses the major causes of organophosphate mortality is respiratory depression. The key role in dealing with organophosphate is the ability for paramedics to recognize early signs and symptoms and early management of patients who need ventilatory support and administration of anticholinergic drugs, as a delay in these processes decreases the chances of a patient to make a full recovery. Ambulance Victoria needs to evaluate their awareness and understanding of organophosphate toxicity due to the increasing rise of organophosphate related deaths and find new ways of improving pre hospital management.