Specialist Questions and Answers

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Question: We are treating a woman with a pulmonary embolus who is a heavy smoker . Can we give a streptokinase injection to this lady & if so, and what dose and how long?
Yes. But it is only recommended when there is cardiovascular compromise (i.e. low output state, sytemic hypotension). The efficacy of thrombolysis in massive PE has been shown in several controlled trials and is as effective as embolectomy. However, the risks may outweigh the benefits. The current recommended regimen is 250000 IU loading dose over 20-30min followed by 100000 IU/hr for 24 hours. Alternatively, 1.5 million units may be used as a single dose. These regimens need not be given directly into the pulmonary artery, but can be given via a peripheral vein.

A more expensive option is to use rtPA (recombinant tissue plasminogen activator). A dose of 0.6mg/kg over 15min followed by 100mg over 2 hours and then full heparinisation until warfarinised. rtPA has the advantage of less risk of anaphylaxis, systemic hypotension and and fewer systemic symptoms. This may be used in haemodynamically stable patients and is better than heparin alone.

For further information and detailed reference list, please see:

BTS Standards of Care Committee. Suspected acute pulmonary embolism: a
practical approach. Thorax 1997; 52 (suppl 4).

Dr Vince Mak, Consultant Physician.

What is the incidence of Pulmonary Embolus in women between the ages of 20 and 30 who are cigarette smokers and who are taking Oral Contraceptives?

There is a slight increased risk (2-4x) in women taking high dose
oestrogen oral contraceptives developing deep vein thrombosis, and thus
by extrapolation, they are at increased risk of PE. However, the
overall risk is still tiny when compared with other aetiologies such as
pregnancy, immobility and pelvic surgery. The combined effect of
smoking is not known but is unlikely to be much more. More frequently
recognised as a predisposing risk factor is the presence of Factor V
Leiden genetic mutation, and there is an additive risk here in young
women on the oral contraceptive pill.

Vince Mak

Further information:

BTS Standards of Care Committee. Suspected Acute Pulmonary Embolism: a
Practical Approach. Thorax 52 (suppl 4) 1997
Grodstein F, Stampfer MJ, Goldharber et al. Prospective study of exogenous hormones and risk of pulmonary embolus in women Lancet 348 (9033):983-7, 1996
Jick H, Derby LE, Myers MW et al. Risk of hospital admission for idiopathic venous thromboembolism among users of postmenopausal oestrogens. Lancet 348 (9033)981-3, 1996
Vandenbroucke JP & Helemrhorst FM. Risk of venous thrombosis with hormone replacement therapy. Lancet 348 (9033); 972, 1996
Ward T. Should oral contraceptive users be screened for factor V Leiden? Oral contraceptives are not the only effective contraceptives BMJ. 315(7099):60, 1997 Jul 5.
van der Meer FJ. Koster T. Vandenbroucke JP. Briet E. Rosendaal FR. The Leiden Thrombophilia Study (LETS). [Review] [18 refs] Thrombosis & Haemostasis. 78(1):631-5, 1997 Jul.
Rintelen C. Pabinger I. Knobl P. Lechner K. Mannhalter C. Probability of recurrence of thrombosis in patients with and without factor V Leiden.
Thrombosis & Haemostasis. 75(2):229-32, 1996 Feb.
Bokarewa MI. Falk G. Sten-Linder M. Egberg N. Blomback M. Bremme K. Thrombotic risk factors and oral contraception.
Journal of Laboratory & Clinical Medicine. 126(3):294-8, 1995 Sep.

Do you know of any relationship between smoking and
insomnia in otherwise "healthy" people.?

This is an interesting question. Smoking has been associated with snoring, (Schmidt-Nomara et al, 1990). Wetter and Young (1994) remarked that there was little epidemiological or clinical information on the relationship between smoking and sleep disturbance. They looked at 3,516 adults as part of a longitudinal, epidemiologic study of sleep-disordered breathing. Symptoms of insomnia, hypersomnia, and parasomnia were assessed using diagnostic criteria from the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., revised). Smoking was associated with difficulty initiating sleep (initial insomnia), and difficulty waking up. Excessive daytime sleepiness was related to smoking in women whilst nightmares and disturbing dreams were related to smoking in men. They concluded that smoking was associated with 'sleep fragmentation'. Sleep disturbance may be more prevalent among smokers due to the stimulant effects of nicotine, nightly withdrawal, an increased prevalence of sleep disordered breathing relative to nonsmokers, and/or an association with psychological disturbance. Pullen et al (1994) found that nicotine patches had the side effect of sleep disturbance.

On the other hand, Prosise et al (1994) examined the effect of smoking withdrawal on sleep quality, daytime sleepiness, and mood in 18 subjects Overnight studies showed a significant increase in the number of relative arousals (a change in sleep stage to wake, stage 1 sleep, or movement), stage changes, and awakenings during smoking cessation. Also during abstinence, the subjects reported that they felt more irritable, had increased feelings of anxiety, felt greater tension, and had more cravings for cigarettes.

The biochemical effects of smoking nicotine involve dose-dependent neurotransmitter and neuroendocrine effects. Circulating levels of norepinephrine and epinephrine increase, and the bioavailability of dopamine is altered as well. Neuroendocrine effects include the release of arginine vasopressin, beta-endorphin, adrenocorticotropic hormone, and cortisol.

Ben Green

Further information:

Prosise GL; Bonnet MH; Berry RB; Dickel MJ. (1994) Effects of abstinence from smoking on sleep and daytime sleepiness.Chest Apr;105(4)
Pullan RD; Rhodes J; Ganesh S; Mani V; Morris JS; Williams GT; Newcombe RG; Russell MA; Feyerabend C; Thomas GA; et al. (1994) Transdermal nicotine for active ulcerative colitis. New England Journal of Medicine Mar 24;330(12):811
Schmidt-Nowara WW; Coultas DB; Wiggins C; Skipper BE; Samet JM. (1990) Snoring in a Hispanic-American population. Risk factors and association with hypertension and other morbidity. Archives of Internal Medicine 1990 Mar;150(3):597-601
Wetter-DW; Young-TB (1994) The relation between cigarette smoking and sleep disturbance. Prev-Med. 23(3): 328-34

Index of Questions

Pulmonary Embolus (and Oral Contraceptives)
Pulmonary Embolus (and Streptokinase) Smoking (and insomnia)

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Last Amended: 23/03/99

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