Studies have sought to delineate the sequence of events following Ivermectin treatment that lead to neurologic SAE and sometimes death, while also trying to understand the mechanisms of adverse reactions to develop more appropriate treatments.In a study looking at mass Ivermectin treatment in Cameroon, one of the greatest endemic regions for both onchocerciasis and loiasis, a sequence of events in the clinical manifestation of adverse effects was outlined.It was noted that the patients used in this study had a L. loa microfilarial load of greater than 3,000 per ml of blood.Within 12–24 hours post-Ivermectin treatment (D1), individuals complained of fatigue, anorexia, and headache, joint and lumbar pain—a bent forward walk was characteristic during this initial stage accompanied by fever. Stomach pain and diarrhea were also reported in several individuals.By day 2 (D2), many patients experienced confusion, agitation, dysarthria, mutism and incontinence. Some cases of coma were reported as early as D2. The severity of adverse effects increased with higher microfilarial loads. Hemorrhaging of the eye, particularly the retinal and conjunctiva regions, is another common sign associated with SAE of Ivermectin treatment in patients with L. loa infections and is observed between D2 and D5 post-treatment. This can be visible for up to 5 weeks following treatment and has increased severity with higher microfilarial loads.Haematuria and proteinuria have also been observed following Ivermectin treatment, but this is common when using Ivermectin to treat onchocerciasis. The effect is exacerbated when there are high L. loa microfilarial loads however, and microfilariae can be observed in the urine occasionally.
An induced coma – also known as a medically induced coma (MIC), barbiturate-induced coma, or drug-induced coma – is a temporary coma (a deep state of unconsciousness) brought on by a controlled dose of an anesthetic drug, often a barbiturate such as pentobarbital or thiopental. Barbiturate comas are used to protect the brain during major neurosurgery, as a last line of treatment in certain cases of status epilepticus that have not responded to other treatments, and in refractory intracranial hypertension following traumatic brain injury. Induced coma usually results in significant systemic adverse effects. The patient is likely to completely lose respiratory drive and require mechanical ventilation; gut motility is reduced; hypotension can complicate efforts to maintain cerebral perfusion pressure and often requires the use of vasopressor drugs. Hypokalemia often results. The completely immobile patient is at increased risk of bed sores as well as infection from catheters. Induced coma is a feature of the Milwaukee protocol, a controversial method that is promoted as a means of treating rabies infection in people. Theory
Barbiturates reduce the metabolic rate of brain tissue, as well as the cerebral blood flow. With these reductions, the blood vessels in the brain narrow, resulting in a shrunken brain, and hence lower intracranial pressure. The hope is that, with the swelling relieved, the pressure decreases and some or all brain damage may be averted.