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Addenbrooke’s Hospital, Cambridge, United Kingdom
Address correspondence to Gilbert Park, MD, FRCA, Addenbrooke’s Hospital, Cambridge CB2 2QQ, UK. Address e-mail to gilbert.park{at}addenbrookes.nhs.uk
Imagine you are in a third-floor flat in a building 200 or 300-years-old. You trip and, unfortunately, break your leg. The ambulance is called. Because the building is so old, the stairs are narrow, winding, and steep; there is no lift. The injury prevents you from getting down the stairs unaided. They are so narrow that only one person can use them at a time, so a stretcher-chair is needed. You are strapped to it so that you cannot fall off it or move, and the feet-first journey downstairs starts. The ambulance men struggle and strain to get you out of the door and onto the stairs. The view is spectacular; you can see the dimly lit stairs all the way down to the basement. You hope that you will not be dropped because it is a long, long way down. As well as the pain, fear causes more adrenaline to be released. If you are young, your body will cope well with the stress, but what if you are elderly, suffering not from a broken leg, but perhaps from a myocardial infarct? Will the increased adrenaline from the fear cause more vasoconstriction and increase the work of the heart, resulting in an increased oxygen demand, more ischemia, and, perhaps, a fatal arrhythmia?
The adverse effects of pain, such as that caused by myocardial infarction, are well reported, but what about those of stress? The effect of psychological stress causing both silent and overt myocardial ischemia has been reported in patients with ischemic heart disease (1). In this issue, Dörges et al. (2) use plasma concentrations of epinephrine and norepinephrine to measure the response to fear in volunteers undergoing simulated medical evacuation.
The simulation consisted of being carried down from a third-floor flat and then driven in an ambulance for 15 min with the sirens going. Some of the volunteers experiencing this were given 25 or 50 µg/kg of midazolam IV, whereas the remainder were given placebo injections. There was also a control group, who sat in a chair for 3 min (representing the period of evacuation down the stairs) and then lay flat on a stretcher for 15 min.
The trip down the staircase resulted in larger concentrations of both catecholamines than the ambulance ride with the sirens on. Epinephrine concentrations were larger in volunteers carried down the staircase than in the control volunteers at all times. The administration of midazolam either abolished or significantly reduced these increases, probably indicating a reduction in stress. However, heart rate did increase in all the groups of volunteers who were stressed, whether they were given midazolam or not. Arterial blood pressure was not different between the groups. Unfortunately, we are not given the effect on level of consciousness, although the plasma concentrations reported would be expected to reduce this.
This study shows that simulated medical evacuation is stressful to volunteers. Unlike patients, they have no injury or life-threatening illness, nor are they leaving their homes or families for a journey to the hospital. The stress the volunteers are experiencing is presumably the fear of being dropped down the stairs. Once in the ambulance they can relax. For patients, we can only assume that the stress of going downstairs is greater and continues once they are in the ambulance. To confirm this, studies would need to be done on patients.
On the face of it, it seems like a good idea to give patients an anxiolytic when they are about to have something frightening done to them. Should the use of anxiolytics be explored more? The answer is yes. It may do patients some good. However, while the idea is attractive, we also need to be aware of the potential problems.
The trial was performed by doctors in a highly controlled situation on volunteers. The real world is not like that. Ambulance personnel or paramedics care for emergency patients in many parts of the world. The environment is often not just difficult, but at times also dangerous. The patients are not always young, but are often elderly, with chronic disease complicating their acute illness. Furthermore, the effect of analgesia on the need for sedation was not explored. The relief of pain may be sufficient for many. No one would disagree that relief of pain has a greater priority than relief of fear. Indeed, opioids will often produce a sense of euphoria, perhaps obviating the need for anxiolysis. In the critically ill, opioids alone may be sufficient in over half of patients when given in adequate amounts (3). In those who do still need anxiolysis, there is the problem of synergy between opioids and drugs such as midazolam (4,5). Although this will improve patient comfort, it will also enhance some of the side effects of both types of drugs. Similar problems may also occur when the benzodiazepines are used with alcohol, even in small doses (6,7). Since alcohol is commonly used in many societies and may contribute to accidents, this interaction is likely to be a problem.
Midazolam or similar drugs would need to be given IV to acutely ill patients, as IM and oral absorption would be too slow and unreliable, although intranasal use has been explored in children (8). All these drugs can have cardiovascular depressant effects (9) that are likely to be worse in patients who are hypovolemic or otherwise compromised (10–12), although these are the patients who may benefit most from the use of anxiolysis. Similarly, respiratory depression may be slight or absent in volunteers (13,14) but may become significant in patients with respiratory disease (15).
These difficulties can cause even an experienced anesthesiologist who uses these drugs for sedation every day to get the dose wrong occasionally. In the operating room, the consequences are usually not life threatening. However, will the ambulance personnel, who may use these drugs only occasionally and in difficult circumstances, be able to retrieve such a situation?
Midazolam is also a potent amnesic drug (16–18), and although the amnesia affects memory only from the time the drug was given, will this place patients at risk of forgetting important parts of their illness? In the elderly it will increase confusion and thus make history-taking more difficult. Indeed, might the depression of consciousness level also confuse clinicians? Given midazolam’s sedative properties, will consent for surgical procedures taken after it is given be viewed as valid? Certainly its administration as a premedicant before surgery may preclude consent being obtained afterward, although in an emergency situation this is less clear (19).
Flumazenil may be used to reverse most of the effects of midazolam (20), although hypotension may still persist. But even this drug has created some difficulties in emergency medicine. Its use in mixed overdoses, causing fits (21,22), increases the potential for such episodes in epileptics who might be receiving benzodiazepines to stop their fits (23). Those patients on chronic benzodiazepine treatment might also suffer an acute withdrawal syndrome if given flumazenil (23,24). These would be extremely difficult situations to control in the field.
There are still many questions that need to be answered before an antianxiolytic is given at the scene routinely. For me, though, if I break my leg in a third-floor flat, morphine followed by perhaps the odd milligram of midazolam would be very nice. I have a fear of writing editorials, but heights scare me more!
References
This article has been cited by other articles:
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  S. Schulz-Stubner Bring the Doctor to the Patient...the German "Notarzt" System Anesth. Analg., March 1, 2003; 96(3): 912 - 912. [Full Text] [PDF]
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