LIFE VOL.1, NO.7 – ATIVAN (LORAZEPAM) AND DISORIENTED DEATH

End of Life No. 7 – I put off adding to the ‘End of Life Issues’ series in ‘Write to the Bone’ when my father passed away – April 23, 2011. As anyone who looses a parent, I’ve had thoughts about that process. I’ll get to them all in time, but for the sake of family and friends, and to allow proper reflection, I wait.

That said, some of my readers may benefit from hearing about a common experience in intensive care units where the elderly have just undergone extensive surgery. In the words of one nurse “we get this all the time”. What she refers to is anxiety, noncompliance, irritability, increased hostility, aggression, angry outbursts, and psychomotor agitation – in short patients that are pissed off and under the influence.

This is how my father behaved some days when given Ativan and other drugs. It was as if he entered a drunken blackout and couldn’t find his way home. The same thing happened with my neighbor’s father later in the summer. The drugs used to reduce the anxiety are powerful benzodiazepines (among other treatments). Imagine tubes and needles strapped to every inch of the body and being unable to move for days on end. Worse, every attempt to make meaning of life is interrupted by pain, loneliness, cognitive confusion and an endless array of strangers prodding, poking and questioning you on an hourly basis. Anxiety is inevitable and staff in the ICU can only deal with so much of that.

The drug I’ve heard most often prescribed is a liberal dose of Ativan. Paradoxically, the anxiety treatment often spawns new levels of anxiety, depression, suicidal ideation, and as mentioned above, deeper discontent and hostility. Family and friends arrive to find a virtual stranger behaving badly. At the moments when we should be saying I love you, I forgive you, I hope you forgive me and love me, everything breaks down. It’s common to hear that “he was not himself”.

This author believes that the administration of some drugs, possibly including Ativan, can backfire on the administrator. It’s meant to calm and control the patient, knock them out a bit if you will, but it also can drive the patient into a physical, mental and spiritual abyss.

I don’t recommend for or against. I’m not qualified. What I can say is that witnessing the distress caused by the use of these drugs has me concerned about my own end of life experience. I avoid alcohol and recreational drugs for a reason. I wouldn’t want anyone in my life today to see me laid out on a hospital bed with catheters and IV lines, especially if confused and in a drug induced hostile blackout.

A disclaimer. Many patients may have wonderful experiences on the same drugs. The point is that if you or your loved one is heading for major surgery, be prepared.

Since I’m not qualified to speak directly to the issue, it will be interesting for you to read copy from Wikipedia (not Mayo Clinic but smarter than I am) on the subject of Lorazepam (marketed as Ativan). If you want to read the full article for yourself visit: (http://en.wikipedia.org/wiki/Lorazepam).

As you scan the following material it may be interesting for you to know that going into surgery my father was in his mid eighties and suffered from glaucoma, sleep apnea, and ataxia (clumsy motion of the limbs and torso, due to failure of gross muscle movement coordination, most evident on standing and walking).

Taken from Wikipedia on Jan. 2, 2012:

Any of the five intrinsic benzodiazepine effects possessed by lorazepam (sedative/hypnotic, muscle relaxant, anxiolytic, amnesic, and anticonvulsant) may be considered as “adverse effects,” or “side effects,” if unwanted.^[5] Adverse effects can include sedation and hypotension; the effects of lorazepam are increased in combination with other CNS depressant drugs.^[7][8]Other adverse effects include confusion, ataxia, anterograde amnesia and hangover effects. With long-term use of benzodiazepines it is unclear whether cognitive impairments fully return to normal after cessation of therapy; cognitive deficits persist for at least 6 months post-withdrawal, but it is possible that longer than 6 months is required for recovery of cognitive function. Lorazepam appears to have more profound adverse effects on memory than other benzodiazepines; lorazepam impairs both explicit memory and implicit memory. In the elderly, falls may occur as a result of benzodiazepines. Adverse effects are more common in the elderly, and they appear at lower doses than in younger patients. Benzodiazepines can cause or worsendepression. Paradoxical effects can also occur, such as worsening of seizures, or paradoxical excitement; paradoxical excitement is more likely to occur in the elderly, children, those with a history of alcohol abuse and in people with a history of aggression or anger problems.^[4] Lorazepam’s effects are dose-dependent, meaning the higher the dose, the stronger the effects (and side effects) will be. Using the smallest dose needed to achieve desired effects lessens the risk of adverse effects.

Sedation is the side effect that most patients complain of. In a group of around 3500 patients treated for anxiety, the most common side effects complained of from lorazepam were sedation (15.9%), dizziness (6.9%), weakness (4.2%), and unsteadiness (3.4%). Side effects such as sedation and unsteadiness increased with age.^[41] Cognitive impairment, behavioural disinhibition and respiratory depression as well as hypotension may also occur.^[23][32]

• Paradoxical effects: In some cases, there can be paradoxical effects with benzodiazepines, such as increased hostility, aggression, angry outbursts, and psychomotor agitation. These effects are seen as more common with lorazepam than other benzodiazepines.^[42] Paradoxical effects are more likely to occur with higher doses, in patients with pre-existing personality disorders and those with a psychiatric illness. It is worth noting that frustrating stimuli may trigger such reactions, even though the drug may have been prescribed to help the patient cope with such stress and frustration in the first place. As paradoxical effects appear to be dose-related, they usually subside on dose reduction or on complete withdrawal of lorazepam.^{[43][44][45][11][46][47]}
• Suicidality: Benzodiazepines may sometimes unmask suicidal ideation in depressed patients, possibly through disinhibition or fear reduction. The concern is that, though relatively nontoxic in themselves^{[verification needed]}, benzodiazepines may inadvertently become facilitators of suicidal behaviour.^[48] Lorazepam should, therefore, not be prescribed in high doses or as the sole treatment in depression, but only with an appropriate antidepressant^[specify].
• Amnesic effects: Among benzodiazepines, lorazepam has relatively strong amnesic effects,^[5][49] but patients soon develop tolerance to this with regular use. To avoid amnesia (or excess sedation) being a problem, the initial total daily lorazepam dose should not exceed 2 mg. This also applies to use for night sedation. Five participants in a sleep study were prescribed lorazepam 4 mg at night, and the next evening three subjects unexpectedly volunteered memory gaps for parts of that day, an effect that subsided completely after 2–3 days’ use.^[50] Amnesic effects cannot be estimated from the degree of sedation present, since the two effects are unrelated.

High dose or prolonged parentally administered lorazepam is sometimes associated with propylene glycol intoxication.^[23][51]

[edit]Contraindications

Lorazepam should be avoided in people with the following conditions:

• Allergy or hypersensitivity – Past hypersensitivity or allergy to lorazepam, to any benzodiazepine, or to any of the ingredients in lorazepam tablets or injections
• Severe respiratory failure – Benzodiazepines, including lorazepam, may depress central nervous system respiratory drive and are contraindicated in severe respiratory failure. An example would be the inappropriate use to relieve anxiety associated withacute severe asthma. The anxiolytic effects may also be detrimental to a patient’s willingness and ability to fight for breath. However, if mechanical ventilation becomes necessary, lorazepam may be used to facilitate deep sedation.
• Acute intoxication – Lorazepam may interact synergistically with the effects of alcohol, narcotics, or other psychoactive substances. It should, therefore, not be administered to a drunk or intoxicated person.
• Ataxia – This is a neurological clinical sign, consisting of unsteady and clumsy motion of the limbs and torso, due to failure of gross muscle movement coordination, most evident on standing and walking. It is the classic way in which acute alcohol intoxication may affect a person. Benzodiazepines should not be administered to already-ataxic patients.
• Acute narrow-angle glaucoma – Lorazepam has pupil-dilating effects, which may further interfere with the drainage of aqueous humour from the anterior chamber of the eye, thus worsening narrow-angle glaucoma.
• Sleep apnea – Sleep apnea may be worsened by lorazepam’s central nervous system depressant effects. It may further reduce the patient’s ability to protect his or her airway during sleep.
• Myasthenia gravis – This condition is characterised by muscle weakness and a muscle relaxant such as lorazepam may exacerbate symptoms.
• Pregnancy and breast feeding – Lorazepam belongs to the Food and Drug Administration (FDA) pregnancy category D, which means that it is likely to cause harm to the developing baby, if taken during the first trimester of pregnancy. There is inconclusive evidence that lorazepam, if taken early in pregnancy, may result in reduced IQ, neurodevelopmental problems, physical malformations in cardiac or facial structure, or other malformations in some newborns. Lorazepam given to pregnant women antenatally may cause floppy infant syndrome^[52] in the neonate, or respiratory depression necessitating ventilation. Regular lorazepam use during late pregnancy (the third trimester), carries a definite risk of benzodiazepine withdrawal syndrome in the neonate. Neonatal benzodiazepine withdrawal may include hypotonia, reluctance to suck, apneic spells,cyanosis, and impaired metabolic responses to cold stress. Symptoms of floppy infant syndrome and the neonatal benzodiazepine withdrawal syndrome have been reported to persist from hours to months after birth.^[53] Lorazepam may also inhibit foetal liver bilirubin glucuronidation, leading to neonatal jaundice. Lorazepam is present in breast milk, so caution must be exercised about breast feeding.