Investigating a Car Crash Case

	 Investigating a Car Crash Case
Questions posed by this case:
Why did the Connie crash the car?
What triggered her status epilepticus?
Was she taking phenytoin at the time, if so why did IT not prevent
her fit?
How did Connie become pregnant if she was taking oral
contraceptives?
phenytoin could phenytoin levels become unstable leading TO seizure? In most patients maintained at a steady dosage, stable phenytoin serum levels are achieved. Patients with unusually low levels may be noncompliant or hypermetabolizers of phenytoin. As phenytoin is highly protein bound, free phenytoin levels may be altered in patients whose protein binding characteristics differ from normal .Determine Connie?s plasma levels, if low, she may not be complying. Since she has been stable for more than two years we can assume she has no protein binding problems. phenytoin ? oral contraceptive interaction Hepatic enzyme-inducing anti-epileptic drugs increase the metabolism of both progesterone and oestrogen. As the concentrations of these hormones may be lowered by 50% or more, adjustments are required in contraceptive regimes to ensure that pregnancy is prevented Oral contraceptives may have increased metabolism by phenytoin, carbamazepine and phenobarbital and therefore may not adequately protect against pregnancy. triggers OF status epilepticus Abrupt withdrawal of phenytoin in epileptic patients may precipitate status epilepticus. When, in the judgment of the clinician, the need for dosage reduction, discontinuation, or substitution of alternative antiepileptic medication arises, this should be done gradually It is important to note that antiepileptic drugs should not be discontinued in patients in whom the drug is administered to prevent major seizures, because of the strong possibility of precipitating status epilepticus with attendant hypoxia and threat to life. rationale for drugs given anti-epileptics Use in Pregnancy-do they harm the fetus? ? A number of reports suggest an association between the use of antiepileptic drugs by women with epilepsy and a higher incidence of birth defects in children born to these women. ? The reports suggesting a higher incidence of birth defects in children of drug-treated epileptic women cannot be regarded as adequate to prove a definite cause and effect relationship. There are intrinsic methodologic problems in obtaining adequate data on drug teratogenicity in humans; genetic factors or the epileptic condition itself may be more important than drug therapy in leading to birth defects. ? The great majority of mothers on antiepileptic medication deliver normal infants. ? In individual cases where the severity and frequency of the seizure disorder are such that the removal of medication does not pose a serious threat to the patient, discontinuation of the drug may be considered prior to and during pregnancy, although it cannot be said with any confidence that even minor seizures do not pose some hazard to the developing embryo or fetus. ? The prescribing physician will wish to weigh these considerations in treating or counseling epileptic women of childbearing potential. ? In addition to the reports of increased incidence of congenital malformations, in children of women receiving phenytoin and other antiepileptic drugs, there have more recently been reports of a fetal hydantoin syndrome. ? This consists of prenatal growth deficiency, microcephaly and mental deficiency in children born to mothers who have received phenytoin, barbiturates, alcohol, or trimethadione. ? However, these features are all interrelated and are frequently associated with intrauterine growth retardation from other causes. ? There have been isolated reports of malignancies, including neuroblastoma, in children whose mothers received phenytoin during pregnancy. ? Arene oxide intermediate metabolites of phenytoin, cabamazepine and phenobarbital may be teratogenic. An animal model exists and in humans, dysmorphology was predicted in 4 of 19 neonates with mothers taking phenytoin. Only these 4 fetuses had low (<30% activity) of the degradative enzyme, epoxide hydrolase, measured in amniocytes (Buehler, 1990). management ? Guidelines for management include early discussion with patient and starting folate 1 mg per day. ? aed monotherapy at lowest dose should be achieved. ? If seizures are not optimally controlled, consider delaying pregnancy to achieve better control. ? Family history should be reviewed for birth defects. Amniocentesis and level II ultrasound at 16-18 weeks are recommended to check for neural tube and cardiac malformations. ? Vitamin K should be given to mother 20 mg/day po from 36th week on, and 1 mg IM to baby at birth. AEDs have been associated with deficiency of Vit K dependent clotting factors resulting in neonatal hemmorhages in abdomen, chest and brain. Clotting times of the of newborn should be checked. ? Maternal aed levels postpartum will increase if dose has been increased during pregnancy and will need to be adjusted downward. ? An increase in seizure frequency during pregnancy occurs in a high proportion of patients, because of altered phenytoin absorption or metabolism. Periodic measurement of serum phenytoin levels is particularly valuable in the management of a pregnant epileptic patient as a guide to an appropriate adjustment of dosage. However, postpartum restoration of the original dosage will probably be indicated. Nursing Mothers ? Infant breast-feeding is not recommended for women taking this drug because phenytoin appears to be secreted in low concentrations in human milk. ? Breast feeding is possible for most infants whose mothers are on AEDs; concentration is lower in breast milk than in maternal plasma, except for ethosuximide in which it is nearly the same, and for valproate, in which it is much lower. ? Sedation may occur in infant from phenobarbital ingestion. ? AEDs cross the placental barrier, and may have prolonged half-lives in the neonate. Sedation or even drug withdrawal may occur with phenobarbital exposure in utero. future management OF epileptic drug regime whilst pregnant ? In general, clearance of AEDs is increased and protein binding is decreased during pregnancy (albumin levels decline). Carbamazepine concentrations decrease slightly in 3rd trimester; free concentration is unchanged. Phenytoin levels decreased significantly throughout pregnancy, but free level is nearly unchanged, therefore the effective level remains fairly stable throughout pregnancy Phenobarbital levels decrease early in pregnancy. ? In general, minor aed dosage adjustments are required if clinical status changes, and should be correlated with free drug levels if possible. ? Monitor levelsapproximately every 4-6 weeks. heparin Does not cross placenta, does not cause fetal bleeding or teratogenicity Rate of major bleeding in pregnancy is about 2%, similar to the risk in non-pregnant patients and with warfarin therapy Heparin requirements appear to increase during pregnancy because of increases in heparin-binding proteins, plasma volume, renal clearance, and heparin degradation by the placenta, which reduces the bioavailability of heparin (12). The major concerns with heparin use during pregnancy are not fetal but maternal and include heparin-induced osteoporosis and heparin-induced thrombocytopenia (hit). indications During pregnancy, women have a fivefold increased risk of venous thromboembolism (vte), compared with nonpregnant women. Pulmonary embolism (PE) is a leading cause of maternal death in the United States (4). The prevalence and severity of this condition warrant consideration of anticoagulant therapy in pregnancy for women at risk for vte. Such therapy includes the treatment of acute thrombotic events, prophylaxis for patients with a history of thrombotic events or identified acquired or congenital thrombophilias, and prevention and treatment of systemic embolization in women with valvular heart disease. Pregnancy-Associated Changes in Coagulation Increases in clotting factors (I, vii, viii, IX, X) Decreases in protein S Decreases in fibrinolytic activity Increased venous stasis Vascular injury associated with delivery Increased activation of platelets Resistance to activated protein C. sodium thiopentone Thiopentone sodium is the most widely used intravenous anaesthetic agent. It leads to a smooth induction in seconds and its effects last for 3-8 minutes. Metabolism is slow (half life of 11 hours) so ?hangover? effects are common and recovery from the induction dose is due to redistribution. It has anticonvulsant but no analgesic properties. It is contraindicated in:
hypovolaemia / shock ? produces cardiorespiratory depression
barbiturate allergy
porphyria
A relative contraindication is significant airways obstruction. Inadvertent intrarterial injection may result in vasospasm, ischaemia and gangrene. Thiopentone Thiopentone diazepam Anxiolytic ? Sedative ? Muscle Relaxant Diazepam is a benzodiazepine with cns depressant properties In high doses, it activates the drug metabolizing enzymes in the liver. With the parenteral form, peak blood levels are reached within 15 minutes after i.v. administration and are of the same magnitude as after oral administration. The respective half-life is approximately 2-3 hours. Diazepam also possesses dependence liability and may produce withdrawal symptoms, but has a wide margin of safety against poisoning. Comparable blood levels of diazepam were obtained in maternal and cord blood indicating placental transfer of the drug. Diazepam may appear in human breast milk. diazepam was shown to be excreted exclusively in the form of its metabolites. The two major metabolites are oxazepam glucuronide and N-desmethylated diazepam. Indications -???? The short-term symptomatic management of mild to moderate degrees of anxiety in conditions dominated by tension, excitation, agitation, fear or aggressiveness, such as may occur in psychoneurosis, anxiety reactions due to stress conditions and anxiety states with somatic expression. As an adjunct for the relief of skeletal muscle spasm due to reflex spasm to local pathology, such as inflammation of the muscle and joints or secondary to trauma; spasticity caused by upper motor neuron disorders, such as cerebral palsy and paraplegia; athetosis and the rare stiff man syndrome. Warnings -??- Pregnancy: Several studies have suggested an increased risk of congenital malformations associated with the use of diazepam, chlordiazepoxide and meprobamate during the first trimester of pregnancy. Therefore, the administration of diazepam is rarely justified in women of childbearing potential. If the drug is prescribed for a woman of childbearing potential, she should be warned to contact her physician regarding discontinuation of the drug if she intends to become or suspects that she is pregnant. future management OF contraception Women on the combined oral contraceptive pill (ocp) who are taking hepatic enzyme-inducing antiepileptic drugs e.g. phenytoin are advised to use a preparation containing at least 50 mcg of oestrogen ? on the basis that a dose of 20 mcg is thought to be necessary to inhibit ovulation ordinarily. This higher dose of oestrogen should be balanced by an increased dose of progesterone. A ?tricycling? with standard (?monophasic tablets?) is recommended (i.e. taking 3 packets without a break followed by a short tablet-free interval of 4 days ? inform the patient that her ?period? will tend to continue into the start of the next pack Epilepsy drugs which do not impair contraceptive efficacy: lamotrigine, vigabatrin, gabapentin, tiagabine, sodium valproate, clobazam, clonazepam Epilepsy drugs which do impair contraceptive efficacy: phenytoin, carbamazepine, oxcarbazepine, phenobarbitone, primidone, topirimate, ethosuximide (possibly) Successful suppression of ovulation should be established by measuring the blood progesterone level ? The progesterone level should not demonstrate the characteristic rise seen during ovulation. For similar reasons, the dose of the progesterone only pill should be at least doubled. status epilepticus Background: The term status epilepticus may be used to describe any continuing type of seizure. Specifically in epileptic cases it involves generalized activity involving all areas of the cortex at once or may spread from a focal area of electrical abnormality when monitored with an electroencephalogram (eeg) or as seen occasionally at the bedside. Traditionally, status epilepticus was defined as 30 minutes of continuous seizure activity or a series of seizures without return to full consciousness between the seizures Pathophysiology: Many of these systemic responses are thought to result from the catecholamine surge that accompanies the condition. Hypertension, tachycardia, cardiac arrhythmias, and hyperglycemia are examples of these systemic effects. Body temperature may increase in patients following the vigorous muscle activity that accompanies gcse. Lactic acidosis is common after a single generalized motor seizure and resolves with termination of the seizure. Most seizures terminate spontaneously. Which processes are involved in seizure termination and why or how these processes fail in status epilepticus is an active area of inquiry. Mortality/Morbidity:
The overall mortality rate is about 20%; death often is related to
an underlying cause of brain injury.
History:
A history of epilepsy frequently is elicited.
Noncompliance with medications is the rule rather than the
exception.
The history may suggest associated injuries, such as a fall or
involvement in a motor vehicle accident.
Physical:
typical rhythmic tonic-clonic activity is present.
Consciousness is impaired.
Rarely, status epilepticus may present as a persistent tonic
seizure.
Suspect subtle status epilepticus in any patient who does not
regain consciousness within 20-30 minutes of cessation of
generalized seizure activity.
Associated injuries that may be present in patients with seizures
include tongue lacerations, shoulder dislocations, head trauma,
and facial trauma.
future management OF epilepsy ? social issues Can Connie drive again? the law Epilepsy is an extremely variable condition but in relation to driving the law does not make a distinction between the different types or causes of epileptic seizures, or between variations in severity, frequency or precipitating factors. However, medical opinion as to your safety as a driver is required. Even free of seizures, you may not be considered for a licence if, for example, your drug treatment causes side-effects which impair your driving ability. Ordinary Driving Licences The current regulations allow an ordinary licence to be granted to people with epilepsy if: i) They have been free from any epileptic seizure (with or without medication) during the period of 1 year from the last seizure until the date when the licence is to have effect, and they are unlikely to be a source of danger to the public. Or ii) If they continue to have seizures but they only occur while asleep and three years have elapsed with no waking seizures, and they are unlikely to be a source of danger to the public If during the period for which your licence is granted epileptic activity recurs you must inform the dvla immediately and stop driving. Even if a seizure happened in conjunction with a change in medication prescribed by your doctor the driving regulations still apply i.e. you must inform dvla and you will probably be required to surrender your licence. It is not why epileptic activity occurs that is legally important ? it is the fact that it takes place. It is important to discuss such an occurrence with your doctor, but it is equally important to remember the responsibility for informing dlva rests with you, not with your doctor.

Investigating a Car Crash Case 8.9 of 10 on the basis of 1929 Review.