How to start an intravenous glyceryl trinitrate (GTN) infusion

How to start an intravenous glyceryl trinitrate (GTN) infusion

Posted in Emergency, Emergency Dept., Medicine, Michael Tam at 20:20 by Michael Tam

Original article: Michael Tam :: Printer friendly
An understanding of how to start and setup an intravenous infusion of glyceryl trinitrate (GTN) is a rather useful skill. Unfortunately, setting up a GTN infusion is sufficiently complicated that it can’t be worked out in an emergency situation. In a nutshell:

Start with glyceryl trinitrate 5 mcg/min then increase infusion rate by 5 mcg/min every 3-5 minutes if needed when infusion rate is GTN 20 mcg/min or more increase infusion rate by 10 mcg/min every 3-5 minutes if needed

GTN infusions are not trivial. Call for help. It should best be performed under the supervision of someone who has experience with them (e.g., a medical registrar or emergency medicine registrar).


Step One: Indications
GTN infusions can be used in the following (1) (2):

hypertensive emergency / malignant hypertension congestive cardiac failure with acute myocardial infarction treatment of angina pectoris not responding to oral nitrates and/or beta blockers control of perioperative hypertension

In hypertensive encephalopathy, aim to reduce the blood pressure slowly (3). There are substantial risks in reducing it quickly.

• reduce the mean arterial pressure by 10% per hour;
• by no more than 25% of the original value.

mean arterial pressure = diastolic + 1/3 (systolic – diastolic)

Step Two: Contraindications
Avoid in the following (1) (2):

hypotension or uncorrected hypovolaemia raised intracranial pressure or cerebral haemorrhage constrictive pericarditis or pericardial tamponade severe anaemia and arterial hypoxaemia concurrent use of phosphodiesterase-5 inhibitors, i.e., sildenafil (Viagra), tadalafil (Cialis) and vardenafil (Levitra)

Step Three: Initial stabilisation
Remember your “ABCs” of emergency management (3):
Position:

• Comfortably;
• in a monitored bed.

Airway:

• Keep patent.

Breathing:

• Administer high flow (i.e., > 6 L/min) via a Hudson mask or non-rebreather mask;
• consider using CPAP if severe pulmonary oedema is present;
• assess respiratory rate and effort (if inadequate, assist with ventilation, e.g., bag-valve-mask with oxygen).

Circulation:

• Measure pulse rate, blood pressure (both arms if thoracic aortic dissection is suspected) and capillary refill;
• attach cardiac monitoring equipment and correct any immediate life threatening arrhythmia;
• insert intravenous cannulae x 2;
• take bloods (FBC, UEC).

Perform a 12-lead ECG
Disability:

• Measure Glasgow Coma Score (GCS); if less than or equal to 8 then consider endotracheal intubation to protect the airway.

Step Four: Draw up and dilute the GTN
GTN is absorbed into many plastics, especially PVC (2). Hence it is important to minimise the amount of tubing / filters in the giving sets and aim to use a glass bottle for dilution.
In Australia, GTN for injection comes in 50 mg/10 mL ampoules.

glyceryl trinitrate 50 mg in 500 mL of 0.9% NaCl solution (glass infusion bottle)

• This yields a concentration of GTN of 100 mcg/mL;
• a solution of 5% dextrose (D-glucose) can be used as an alternative.

Step Five: Start infusion
The dose of GTN needs to be carefully titrated for the patient according to response. The starting dose is low:

glyceryl trinitrate 5 mcg/min which is 3 mL/h of the dilution (glyceryl trinitrate 100 mcg/mL)

Step Six: Upward titration
Start with small increases up to GTN 20 mcg/mL:

Increase infusion rate by glyceryl trinitrate 5 mcg/min every 3-5 minutes. which is 3 mL/h of the dilution (glyceryl trinitrate 100 mcg/mL) every 3-5 minutes

When the infusion rate of GTN is greater than of equal to 20 mcg/mL (i.e., from the forth upward titration and beyond):

Increase infusion rate by glyceryl trinitrate 10 mcg/min every 3-5 minutes. which is 6 mL/h of the dilution (glyceryl trinitrate 100 mcg/mL) every 3-5 minutes

• There is no real maximum dose and the infusion rate should be adjusted to effect;
• GTN has a wide therapeutic range;
• it is suggested by McCowan and Shapiro (2006) (1) that the maximum rate to be GTN 200 mcg/min.

Step Seven: Arrange for definitive care
Once the patient has been stabilised, definitive care should be arranged. For a patient who requires a GTN infusion, this will be a monitored bed (i.e., a coronary care unit, intensive care unit or at least, a monitored bed).

Discussion

• Beware in severe hypertension following head injury, intracranial bleed or cerebrovascular accident. The hypertension is in part the body’s response to maintain cerebral perfusion.
• Some patients may respond fully to even the starting infusion rate of GTN (5 mcg/min) so careful titration and monitoring is required.
• For patients requiring a high infusion dose of GTN, it can be helpful to increase the concentration of the infusion solution and then use the appropriate rate.

Reference articles
(1) McCowan C., Shapiro N. Hypertensive Emergencies. Emedicine. Last updated 13 April 2006. [Link]
(2) Glyceryl Trinitrate Concentrate Injection (DBL). MIMS Online. Last updated 13 September 2005.
(3) Hypertensive Emergencies, Treatment. Emergency Life Support (ELS) Course Manual. Second Edition. 2002.

Ibuprofen Use Linked to Reduced Parkinson's Disease Risk

 

February 18, 2010 — A new prospective analysis using data on more than 136,000 people participating in the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS) suggests that use of ibuprofen, but not other nonsteroidal anti-inflammatory drugs (NSAIDs), is associated with a reduction in Parkinson's disease (PD) risk on the order of 40%.
Neuroinflammation is thought to play a role in PD, said lead author Xiang Gao, MD, from Harvard School of Public Health, Boston, Massachusetts, "but our results showed only ibuprofen and not other agents seems to be protective for PD.
"This suggests that specific effects of ibuprofen not shared by other NSAIDs play a role in this protective effect, but we don't know the exact mechanism at this time," Dr. Gao told Medscape Neurology.
The results were published online February 17 in advance of their presentation at the upcoming American Academy of Neurology 62nd Annual Meeting in Toronto, Ontario, Canada, April 10-17, 2010. The abstract is posted at www.aan.com.
Addressing Neuroinflammation?
Neuroinflammation may contribute to the pathology of Parkinson's disease, the study authors note, and use of NSAIDs in general, and ibuprofen in particular, has previously been linked to reduced risk of the disease. For example, a previous paper presented by Dr. Gao's Harvard School of Public Health colleague Albert Ascherio, MD, using data from the American Cancer Society's Cancer Prevention Study II Nutrition Cohort, showed that ibuprofen users had a reduced PD risk of about 35%.
In the present study, Dr. Gao and colleagues analyzed data on 136,197 men and women included in the prospective cohorts of the NHS of women and the HPFS of men who were free of PD and other diseases at baseline in 1998 for the NHS and 2000 for the HPFS. The use of NSAIDs was assessed by questionnaire.
During 6 years of follow-up, there were 291 incident cases of PD. The study authors report that users of ibuprofen had a significantly lower risk of developing PD than nonusers and, further, that there was a dose-response relationship between the number of tablets taken per week and PD risk (P for trend = .01)
Table 1. Risk for Parkinson's Disease for Ibuprofen Users vs Nonusers

Comparison	Relative Risk (95% CI)	P Value
Ibuprofen use vs nonuse	0.62 (0.42 – 0.92)	.02

CI = confidence interval
Conversely, there was no significant relationship between use of aspirin, other NSAIDs, or acetaminophen and PD risk.
Table 2. Risk for Parkinson's Disease Associated With Use of Other Pain Relievers

Pain Reliever	Relative Risk	P Value
Aspirin	0.98	.86
Other NSAIDs	1.26	.24
Acetaminophen	0.87	.39

NSAIDs = nonsteroidal anti-inflammatory drugs
They also performed an additional meta-analysis of 5 prospective studies, Dr. Gao added. "We found similar results," he said. "The use of ibuprofen is associated with around 30% lower risk of PD in this meta-analysis."
Table 3. Meta-Analysis: Risk for PD With Ibuprofen Use vs No Ibuprofen Use

Comparison	Relative Risk (95% CI)	P Value
Ibuprofen use vs nonuse	0.73 (0.63 – 0.85)	< .001

CI = confidence interval
Dr. Gao said it will be important to have these findings confirmed in other independent populations and would like to see whether ibuprofen might also affect disease progression in people who already have PD.
First though, he said, "I think the most important thing is to try and find out the mechanism; why ibuprofen is protective against Parkinson's disease."
Extension of Earlier Studies
Asked for comment on these findings, Kapil Sethi, MD, professor of neurology and director of the Movement Disorders Program at the Medical College of Georgia in Augusta and a member of the Medscape Neurology editorial advisory board, said these findings are an extension of earlier studies documenting an inverse relationship between use of anti-inflammatory drugs and PD.
"However, the reduced risk was associated only with the use of ibuprofen and not the other [NSAIDs], suggesting that it is the drug and not the underlying conditions for which the [NSAIDs] are administered that is responsible for the risk reduction," Dr. Sethi noted.
"The relative number of individuals treated with ibuprofen vs the other agents is not mentioned in the news release," he added, "but we look forward to the complete report."
The study was funded by grants from the National Institutes of Health/National Institute of Neurological Disorders and Stroke. The study authors have disclosed no relevant financial relationships.
American Academy of Neurology (AAN) 62nd Annual Meeting: Abstract 1347. Presented April 10-17, 2010.

North American Menopause Society Issues Guidelines on Hormone Therapy Laurie Barclay, MD

North American Menopause Society Issues Guidelines on Hormone Therapy

Laurie Barclay, MD

February 18, 2010 — The benefit-risk ratio for menopausal hormone therapy (HT) is favorable for women beginning HT close to menopause but decreases in older women and with time since menopause in previously untreated women, according to the latest evidence-based position statement of the North American Menopause Society (NAMS), posted online February 16 and will be published in the March/April issue of Menopause.
"From a clinical perspective, the latest NAMS position statement on HT considers the current best practice of medicine," NAMS Executive Director Margery L. S. Gass, MD, NCMP, said in a news release. "The Panel of world famous authorities clarified a broad spectrum of topics related to HT benefits and risks for postmenopausal women."
Development of the Guidelines
The goal of the latest guidelines was to update clinicians as well as the lay public regarding NAMS' recommendations for menopausal HT for postmenopausal women, considering the therapeutic benefit-risk ratio at various times through and beyond menopause.
An advisory panel of 17 clinicians and researchers with special expertise in HT reviewed each section of the previous position statement, published by NAMS in July 2008, in light of new studies and findings, and reached consensus on recommendations. The NAMS board of trustees then approved the updated official position statement, which highlights recent evidence regarding risks for breast cancer, cognitive dysfunction and decline, dementia, coronary heart disease (CHD), and stroke, as well as new recommendations regarding discontinuing HT.
The updated guidelines also include new sections on HT and ovarian and lung cancer, a listing of areas that vary from the 2008 position statement, and a suggested bibliography of key references published since the last statement.
The American Medical Women's Association, the Asociación Mexicana para el Estudio del Climaterio, the Endocrine Society, Healthy Women (formerly the National Women's Health Resource Center), the National Association of Nurse Practitioners in Women's Health, and the Society of Obstetricians and Gynaecologists of Canada all had representatives participating fully in the editorial process and have endorsed the newest NAMS position statement.
"Current evidence supports a consensus regarding the role of HT in postmenopausal women, when potential therapeutic benefits and risks around the time of menopause are considered," the statement authors write. "Recent data support the initiation of HT around the time of menopause to treat menopause-related symptoms; to treat or reduce the risk of certain disorders, such as osteoporosis or fractures in select postmenopausal women; or both. The benefit-risk ratio for menopausal HT is favorable for women who initiate HT close to menopause but decreases in older women and with time since menopause in previously untreated women."
The Women's Health Initiative (WHI) trial of estrogen therapy (ET) offered evidence of considerable safety for 0.625 mg/day of oral conjugated estrogen, supporting the position that at least for this form of HT, the potential absolute risks are low.
In the WHI trial of combined estrogen-progestogen therapy (EPT), most risks were determined to be rare, using the criteria of the Council for International Organizations of Medical Sciences, except for stroke, which was above the rare category.
"For women younger than age 50 or those at low risk of CHD, stroke, osteoporosis, breast cancer, or colon cancer, the absolute risk or benefit from ET or EPT is likely to be even smaller than that demonstrated in the WHI, although the relative risk at different ages may be similar," the statement authors write. "There is a growing body of evidence that each type of estrogen and progestogen, route of administration, and timing of therapy has distinct beneficial and adverse effects. Further research remains essential."
Cancer and HT
Evidence to date is conflicting regarding the role of HT and risk for ovarian cancer, with no association or a modest increase in most epidemiologic studies, but with an association between HT use and increased ovarian cancer risk based on a relatively large volume of observational trial data. The statement suggests that the association between ovarian cancer and HT beyond 5 years, if any, should be considered as rare or very rare, but that women with a positive family history or other increased risk for ovarian cancer should be counseled about this rare association.
Overall data, including those from WHI analysis, suggest that starting EPT in older women with a positive smoking history may promote the growth of existing lung cancers. In contrast, evidence from the WHI and some case-control and cohort studies suggests that use of HT in women younger than 60 years offers some protection against lung cancer.
Although safety of EPT in survivors of breast cancer is controversial, with observational studies suggesting that it is safe and possibly even protective against recurrence, a randomized controlled trial showed a statistically significant 2.4-fold increase in new breast cancer events. ET use in breast cancer survivors has not been proven to be safe and may be associated with an increased risk for recurrence.
Cognitive Impairment, CHD, and HT
For the sole or main indication of preventing cognitive aging or dementia, the statement does not recommend HT at any age, and HT is actually linked to increased incidence of dementia when started in women age 65 years and older. Available data do not adequately address whether HT started soon after menopause increases or decreases later dementia risk, and limited evidence does not support the use of HT as a treatment of Alzheimer's disease.
In terms of cardiovascular effects, the statement authors note that HT is currently not recommended as a sole or main indication for coronary protection in women of any age. Starting HT by age 50 to 59 years or within 10 years of menopause to treat typical menopausal symptoms does not seem to increase the risk for CHD events, and there is some recent evidence that starting ET in early postmenopause may lower CHD risk.
Findings of observational studies have been inconsistent regarding stroke risk with HT. The Nurses Health Study and WHI showed an increased risk for ischemic stroke, but other studies showed no effect on stroke risk.
Current data suggest that when HT is either tapered or abruptly discontinued, rates of vasomotor symptom recurrence are similar. The statement therefore makes no recommendation concerning how to discontinue therapy.
"When HT is desired by patients, individualization of therapy is key to providing health benefits with minimal risks, thereby enhancing [quality of life]," the statement authors conclude. "Women should be informed of known risks, but it cannot be assumed that benefits and risks of HT apply to all age ranges and durations of therapy. A woman's willingness to accept risks of HT will vary depending on her individual situation, particularly whether HT is being considered to treat existing symptoms or to lower risk for osteoporotic fractures that may or may not occur."

Weekly Vitamin D3 Improves Vitamin D Insufficiency but Not Neuromuscular Function in Older Adults

 

Laurie Barclay, MD

Authors and Disclosures 

February 18, 2010 — Weekly treatment with 8400 IU of vitamin D₃ raises serum 25-hydroxyvitamin D [25(OH)D] concentrations in elderly, vitamin D–insufficient individuals, according to the results of a randomized controlled, double-blind trial reported online February 3 in the American Journal of Clinical Nutrition.
"Vitamin D insufficiency, which is prevalent in older individuals, is associated with bone and muscle weakness and falls," write Paul Lips, from Vrije Universiteit Medisch Centrum, Amsterdam, Netherlands, and colleagues. "We examined the effects of a weekly dose of 8400 IU vitamin D₃ on postural stability, muscle strength, and safety."
Participants 70 years or older with 25(OH)D concentrations of 20 ng/mL or less but at least 6 ng/mL were randomly assigned to receive a weekly dose of 8400 IU of vitamin D₃ or placebo. The main endpoint of the study was mediolateral body sway with eyes open, measured with use of the AccuSwayPLUS platform (Advanced Medical Technology Inc, Watertown, Massachusetts). The short physical performance battery and serum 25(OH)D concentrations were secondary outcomes. Safety and tolerability were evaluated, and treatments were compared by use of an analysis of covariance model.
Strength of Randomized Study Design
"An increasing number of studies report on significant associations between low serum levels of 25-hydroxyvitamin D (25-(OH)D) and a multitude of extra-skeletal diseases and pathological conditions," Meinrad Peterlik, PhD, MD, professor emeritus of pathophysiology at Medical University Vienna in Vienna, Austria, told Medscape Nutrition when asked for independent comment.
"However, these mostly observational studies are rarely controlled for potential confounders, and interventional trials that would prove a causative relation between a compromised vitamin D status and disease incidence are rare. The main strength of the study by Lips et al. thus lies in the fact that it was designed as a randomized controlled multicenter trial to evaluate the effect of vitamin D₃ supplementation on a well defined neuromuscular functional parameter, i.e., body sway, in a group of elderly people with sub-optimal vitamin D supply."
In patients treated with 8400 IU of vitamin D₃ (n = 114) but not in patients receiving placebo (n = 112), serum 25(OH)D concentrations increased significantly from 13.9 to 26.2 ng/mL (P < .001). Mediolateral sway and short physical performance battery at 16 weeks were not significantly different between treatment groups.
Treatment with 8400 IU of vitamin D₃ was associated with significantly decreased sway vs treatment with placebo (P = .047) in patients with elevated baseline sway but not in patients with normal baseline sway, based on a post hoc analysis of patients subgrouped by baseline sway (≥ 0.46 vs < 0.46 cm).
"Weekly treatment with 8400 IU vitamin D₃ raised 25(OH)D concentrations in elderly, vitamin D–insufficient individuals," the study authors write. "Treatment with 8400 IU vitamin D₃ did not reduce mediolateral sway significantly compared with treatment with placebo in this population, although in post hoc analysis, treatment with 8400 IU vitamin D₃ reduced sway in the subgroup of patients who had elevated sway at baseline. Weekly treatment with 8400 IU vitamin D₃ was well tolerated."
Parathyroid hormone levels decreased significantly in the vitamin D₃ group but not in the placebo group. Both groups had similar adverse events and incidences of hypercalcemia, hypercalciuria, and elevated creatinine levels.
Limitations of the Study
"Although the results are straightforward, their interpretation is hampered by a number of facts, most of which are appropriately addressed by the authors themselves," Dr. Peterlik told Medscape Nutrition. "However, they fail to discuss what impact the optimization of calcium intake in the entire study group could have had on the outcome of the study. It could well be that at high calcium intake levels vitamin D supplementation is only minimally effective. This would not be surprising since a recent study by one of the coauthors (Pfeifer et al., Osteoporosis Int. 20:315-322, 2009) shows a positive effect of combined vitamin D and calcium supplementation on parameters of muscle function in elderly people."
Limitations acknowledged by the study authors include small size and unusually healthy condition of the elderly participants. In addition, a substantial number of participants had mediolateral sway values at baseline that were consistent with participants who did not fall, suggesting that their balance as measured by sway was adequate. There may have been little room for improvement of sway and physical performance with treatment in these patients.
"It is clear that elderly individuals with an increased body sway will benefit from a daily dose of 1200 IU vitamin D₃ in combination with intake of > 1000 mg calcium per day," Dr. Peterlik concluded. "Additional studies with fracture rates as endpoint are necessary to prove that the observed reduction of body sway actually has a substantial impact on the incidence of falls and osteoporotic fractures in elderly people."
Merck & Co Inc supported this study, employs 5 of the study authors, and provided research grants to 4 other study authors. Dr. Peterlik has disclosed no relevant financial relationships.
Am J Clin Nutr. Published online February 3, 2010.

Pandemic H1N1 Virus Should Be Added to 2010-2011 Seasonal Influenza Vaccine, Says WHO

Robert Lowes

Authors and Disclosures 

February 18, 2010 — The World Health Organization (WHO) recommended today that the 2010-2011 seasonal influenza vaccines for the northern hemisphere should include a strain of the "dominant" pandemic A (H1N1) virus, as well as 2 nonpandemic influenza strains.
National public health authorities will decide whether to include a strain of the pandemic virus in the traditional trivalent vaccine or administer it separately as a monovalent vaccine, said Keiji Fukuda, MD, MPH, the special pandemic influenza advisor to the WHO director-general, at a press conference today.
WHO is dropping the older, nonpandemic seasonal A (H1N1) virus strain from its recommended mix because it does not expect this strain to circulate at significant levels.
The decision to replace the nonpandemic A (H1N1) strain with a pandemic strain was based on input from a WHO advisory committee composed of experts mostly from the laboratories and national public health agencies that make up the WHO Global Influenza Surveillance Network.
"In essence, what the scientists said was that in the past year, the overwhelming number of influenza viruses isolated around the world were the pandemic H1N1 virus," said Dr. Fukuda. "The experts believe, based on this information, that these viruses will continue to be one of the dominant viruses in the coming fall and winter season in the northern hemisphere."
Trivalent Vaccine with Pandemic Strain Makes Sense for Countries "That Use a Lot of Seasonal Flu Vaccine"
The 3 influenza strains recommended by WHO for northern hemisphere vaccines are an 

1) A/California/7/2009 (H1N1)–like virus, which is a pandemic strain; an 
2) A/Perth/16/2009 (H3N2)–like virus; and a 
3) B/Brisbane/60/2008-like virus.

In September 2009, WHO recommended these same strains for seasonal influenza vaccines for the southern hemisphere in 2010. WHO issues these recommendations for vaccine composition each September and February for the southern and northern hemispheres, respectively, for the coming influenza season.
If national public health authorities choose to use the pandemic strain for a monovalent vaccine, then the other 2 strains could make up a second vaccine.
Dr. Fukuda said a trivalent vaccine containing the pandemic virus would make sense for countries "that use a lot of seasonal flu vaccine."
Vaccine manufacturers and national governments, he said, would theoretically be able to use their current stockpiles of pandemic vaccines in bulk form for 2010-2011 seasonal vaccines in a trivalent formulation. In contrast, pandemic vaccine already packaged in vials and syringes could not be reused.
Dr. Fukuda emphasized that the recommendation to give seasonal-vaccine status to the pandemic influenza virus does not mean that the current pandemic is over. However, a WHO emergency committee will convene next week to decide whether the pandemic has entered an official "postpeak period," which means the worst is over, although the pandemic virus continues to cause sickness and even cause outbreaks in new regions. As proof, Dr. Fukuda noted that WHO has received new reports this week of communitywide transmission of the pandemic virus in Mauritania, which comes on the heels of outbreaks in neighboring Senegal.

Transdermal Nicotine for 24 Weeks vs 8 Weeks May Improve Abstinence CME/CE

 

February 2, 2010 — Transdermal nicotine for 24 weeks compared with 8 weeks is more effective in achieving and maintaining abstinence and reduces the risk for lapses in smoking, according to the results of a parallel randomized, double-blinded, placebo-controlled trial reported in the February 2 issue of the Annals of Internal Medicine.
"Tobacco dependence is a chronic, relapsing condition that may require extended treatment," write Robert A. Schnoll, PhD, from the University of Pennsylvania in Philadelphia, and colleagues. "We evaluated the relative efficacy of extended (24 weeks) versus standard (8 weeks) transdermal nicotine therapy for promoting biochemically confirmed point-prevalence abstinence at weeks 24 and 52 among adult smokers."
From September 2004 to February 2008, a total of 568 adult smokers seen at an academic center were randomly assigned to standard therapy (Nicoderm CQ [GlaxoSmithKline, Research Triangle Park, North Carolina], 21 mg, for 8 weeks and placebo for 16 weeks) or extended therapy (Nicoderm CQ, 21 mg, for 24 weeks), with use of an unstratified small block–randomization scheme.
The main endpoint of the study was biochemically confirmed point-prevalence abstinence at weeks 24 and 52, and secondary endpoints were continuous and prolonged abstinence, lapse and recovery events, cost per additional quitter, adverse effects, and adherence.
Compared with standard therapy, extended therapy was associated with higher rates at week 24 of point-prevalence abstinence (31.6% vs 20.3%; odds ratio [OR], 1.81; 95% confidence interval [CI], 1.23 - 2.66; P = .002), prolonged abstinence (41.5% vs 26.9%; OR, 1.97; CI, 1.38 - 2.82; P = .001), and continuous abstinence (19.2% vs 12.6%; OR, 1.64; CI, 1.04 - 2.60; P = .032). The extended therapy group also had lower risk for lapse (hazard ratio [HR], 0.77; 95% CI, 0.63 - 0.95; P = .013), higher likelihood of recovery from lapses (HR, 1.47; 95% CI, 1.17 - 1.84; P = .001), and slower time to relapse (HR, 0.50; 95% CI, 0.35 - 0.73; P < .001).
However, at week 52, extended therapy was associated with higher quit rates only for prolonged abstinence (P = .027). The extended-treatment evaluation revealed no between-group differences in adverse effects and adverse events.
"Transdermal nicotine for 24 weeks increased biochemically confirmed point-prevalence abstinence and continuous abstinence at week 24, reduced the risk for smoking lapses, and increased the likelihood of recovery to abstinence after a lapse compared with 8 weeks of transdermal nicotine therapy," the study authors write. "Additional research on the optimal duration of therapy and the possible addition of other treatment components (for example, more intensive counseling, precessation use of nicotine patches) from an efficacy, patient acceptance, and cost perspective should be a priority."
Limitations of this study include low generalizability because participants were smokers without medical comorbid conditions who were seeking treatment, and also there were differences in adherence between treatment groups.
"Some participants did not provide complete abstinence data," the editors write. "Extended therapy with transdermal nicotine helps some adults quit smoking, but benefits may persist only while treatment is maintained."
The National Cancer Institute and the National Institute on Drug Abuse, National Institutes of Health, supported this study. The senior study author (Caryn Lerman, PhD) has disclosed various financial relationships with GlaxoSmithKline, AstraZeneca, Pfizer, and Novartis.
Ann Intern Med. 2010;152:144-151.
Additional Resources
Futher information on tobacco cessation programs for healthcare professionals to access and for clinicians to distribute to patients is available online.

Clinical Context

Transdermal nicotine therapy has been demonstrated to help cigarette smokers quit, and current guidelines recommend 8 weeks of treatment for patients attempting smoking cessation. The authors of the current research hypothesize that a longer duration of treatment with transdermal nicotine therapy might improve smoking cessation outcomes, although a previous trial comparing 8 weeks vs 22 weeks of transdermal nicotine therapy found no difference in the rate of continuous abstinence from smoking between groups.
The current study compares transdermal nicotine therapy for 8 weeks vs a treatment duration of 24 weeks, and it features a dosing methodology as well as outcome assessment that differs from the previous trial.

Study Highlights

• Study subjects were recruited at 1 academic center among adults between the ages of 18 and 65 years who smoked at least 10 cigarettes daily for the last year. Patients with significant medical or psychiatric illness were excluded from the study protocol.
• Participants were randomly assigned to receive 21-mg transdermal nicotine patches for 24 weeks, or 8 weeks of active patches plus 16 weeks of placebo patches. The patches were changed every 24 hours, and there was no tapering at the end of treatment.
• All participants received 8 behavioral counseling visits to stop smoking. Transdermal nicotine therapy was initiated on a prearranged quit date.
• The primary study outcome was 7-day point prevalence abstinence from smoking at study weeks 24 and 52, which was verified with exhaled carbon monoxide levels. Researchers also followed rates of continuous abstinence and time to relapse.
• 568 smokers provided data for study analysis. The mean age of participants was 44.8 years, and 44.7% of the study cohort consisted of women. The mean number of cigarettes smoked per day was 21.2.
• Study completion rates were higher at 24 weeks in comparing the extended therapy group vs the standard therapy group (91% vs 83%, respectively) but were similar at week 52. Adherence to study patches at 24 weeks was 25% and 40% in the standard and extended therapy groups, respectively.
• Point-prevalence abstinence rates at week 24 favored extended treatment vs standard therapy (31.6% vs 20.3%, respectively), whereas this outcome was similar between groups at week 52 (14.5% and 14.3%, respectively).
• Rates of abstinence from the quit date to week 24 (continuous abstinence) were also higher in the extended treatment group, but this result did not remain valid at week 52. Prolonged abstinence between study groups between weeks 2 and 52 was superior in the extended therapy group vs the standard treatment group.
• Extended nicotine therapy was also associated with a longer time to relapse between weeks 9 to 24 and increased speed of recovery from relapse during this period.
• There were 3 serious adverse events in the extended therapy group and 1 serious adverse event in the standard therapy group. All of these events occurred before 8 weeks. Rates of other adverse events were generally similar between randomized groups.
• The incremental cost of extended vs standard therapy was $2482 for each additional quitter gained through a longer duration of treatment.

Clinical Implications

• The current recommended treatment duration of transdermal nicotine therapy for smoking cessation is 8 weeks.
• In the current study, extended treatment with transdermal nicotine therapy for 24 weeks was associated with improved point-prevalence abstinence and continuous abstinence rates vs standard therapy at 24 weeks, but not at 52 weeks. Extended therapy also improved the time to relapse during active treatment vs placebo.

CME Test

Questions answered incorrectly will be highlighted.

What is the current recommended duration of transdermal nicotine therapy for smoking cessation?

2 weeks

4 weeks

6 weeks

8 weeks

All of the following outcomes were improved with extended duration vs standard transdermal nicotine therapy in the current study by Schnoll and colleagues except:

Point-prevalence abstinence at 24 weeks

Point-prevalence abstinence at 52 weeks

Continuous abstinence at 24 weeks

Slower time to relapse from 9 to 24 weeks

 

Management of Acute Poisoning From Medication Ingestion Reviewed CME/CE

Target Audience

This article is intended for primary care clinicians, emergency medicine specialists, and other specialists who provide care to adults and children after acute medication poisoning.

Goal

The goal of this activity is to provide medical news to primary care clinicians and other healthcare professionals in order to enhance patient care.
...

February 8, 2010 — Family physicians should be familiar with treatment of accidental and intentional medication ingestions, according to a review of the management of acute poisoning caused by medication ingestion published in the February 1 issue of American Family Physician.
"Poisoning from medications can happen for a variety of reasons, including intentional overdose, inadvertently taking an extra dose, dispensing or measuring errors, and exposure through breast milk," write Ivar L. Frithsen, MD, and William M. Simpson, Jr, MD, from Medical University of South Carolina in Charleston.
"The most common medication poisonings in adults (in order of prevalence) include analgesics; sedatives, hypnotics, and antipsychotics; antidepressants; cardiovascular drugs; anticonvulsants; antihistamines; hormones and hormone antagonists; antimicrobials; stimulants and illicit drugs; cough and cold preparations; muscle relaxants; topical preparations; gastrointestinal preparations; and miscellaneous drugs," Drs. Frithsen and Simpson write. "The most common medication poisonings in children (in order of prevalence) include analgesics; topical preparations; cough and cold preparations; vitamins; antihistamines; gastrointestinal preparations; antimicrobials; hormones and hormone antagonists; electrolytes and minerals; cardiovascular drugs; dietary supplements, herbal medications, and homeopathic medications; asthma therapies; antidepressants; and sedatives, hypnotics, and antipsychotics."
In the United States, several million episodes of poisoning are reported each year, causing significant morbidity and mortality rates. Nearly one half of all poisonings reported in the United States are attributed to acute medication poisonings, which should be considered in patients with an acute change in mental status.
Steps in Treatment of Poisoning
The first steps in treatment of a patient who has been poisoned are to evaluate the airway, breathing, and circulation, and to perform a complete history. Poisoning with drugs from certain classes, notably anticholinergics, cholinergics, opioids, and sympathomimetics, are associated with constellations of symptoms known as toxidromes. For example, anticholinergic poisoning is associated with delirium; hyperthermia; ileus; mydriasis; tachycardia; urinary retention; and warm and dry skin.
For identification of electrolyte imbalances and/or impairment of liver and renal function, basic laboratory studies, such as a complete metabolic profile, are an important part of the workup for possible medication poisonings. Clinical presentation and history should help determine what other laboratory studies are indicated.
Unless a specific antidote is available, management is supportive in most cases, because less than 1% of poisonings are fatal. Although single-dose activated charcoal is the preferred modality of gastrointestinal tract decontamination, it should not be used in all patients. The review includes specific therapies for acute medication poisoning based on the type of drug ingested.
For unstable patients who have ingested toxic medications, ongoing treatment should aim to correct hypoxia and acidosis and to maintain adequate circulation. Even when these patients appear to be compensating, their mental or hemodynamic status may deteriorate rapidly. Children are particularly susceptible to profound effects from even small amounts of medication.
Multiple factors, including pharmacokinetics of the ingested substance and the ability to be monitored in the home environment, must be considered in the disposition of a person who has been poisoned. Longer monitoring is required for patients with signs or symptoms of toxicity. For patients who have attempted suicide, psychiatric evaluation and often psychiatric hospitalization are indicated. Counseling referral is recommended for patients with evidence of substance abuse.
Key Recommendations
Specific key clinical recommendations for practice, and their accompanying level of evidence rating, are as follows:

• For most medication ingestions, single-dose activated charcoal is the modality of choice for gastrointestinal decontamination. This treatment can generally be used up to 1 hour after ingestion of a potentially toxic amount of medication (level of evidence, C).
• There is no indication for using ipecac syrup in a healthcare setting (level of evidence, C).

"For unstable patients, admission to an intensive care unit is appropriate, and transfer to a tertiary care facility should be considered, especially with children," the review authors conclude. "For stable patients, the amount of observation time is based on the half-life of a medication, the amount ingested, and the formulation. Any patient who develops signs or symptoms of toxicity that do not reverse during the observation period should be admitted for further observation."
The review authors have disclosed no relevant financial relationships.
Am Fam Physician. 2010;81:316-323. Abstract
Additional Resource
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Clinical Context

According to the American Association of Poison Control Centers' report by Bronstein and colleagues in the December 2007 issue of Clinical Toxicology, more than 2.4 million poisoning exposures were reported in the United States in 2006. Almost half of poisoning exposures were from prescription and over-the-counter medications.
This summary addresses the management of acute poisoning from medication ingestion.

Study Highlights

• The poison control center can assist with management on the telephone, at the office, or in the hospital.
• Mortality rate is less than 1% from acute poisoning.
• In patients with acute change in mental status, medication poisoning should be suspected based on acute behavioral changes, concern of others, and evidence of ingestion.
• Initial approach includes assessment of airway, breathing, circulation; thorough history; and inspection for transdermal patches.
• Important information includes time, identification, and amount of medication.
• The gastrointestinal decontamination method of choice in most cases is activated charcoal within 1 hour of ingestion except in cases of decreased level of consciousness, low affinity of ingested medication for binding charcoal, and increased risk of gastrointestinal bleeding or perforation.
• Other methods of gastrointestinal decontamination (in order of most to least used) are gastric lavage, cathartics, and whole-bowel irrigation.
• Ipecac syrup has no role in the healthcare or home setting.
• Basic symptom management includes Trendelenburg position and fluid resuscitation for hypotension, stimulation for apnea or lethargy, warming measures for hypothermia, and cooling measures for hyperthermia.
• Complete metabolic profile can assess electrolytes and liver and renal function.
• General toxicology screen is not helpful in immediate treatment.
• Quantitative drug levels should be ordered based on history and signs and symptoms of ingestion of acetaminophen, carbamazepine, digoxin, ethanol, iron, lithium, phenobarbital, phenytoin, salicylates, theophylline, and valproate.
• Serum N-acetyl-para-aminophenol levels should be checked in all unknown ingestions.
• Arterial or venous blood gas analysis can identify acidosis and hypoxia.
• Electrocardiography can assess arrhythmias.
• Chest radiography can assess pulmonary edema.
• Medications associated with certain signs and symptoms are acetaminophen, benzodiazepines, beta-blockers, calcium channel antagonists, clonidine, opioids, salicylates, sulfonylureas, and tricyclic antidepressants.
• Specific medications have toxidromes or certain types of symptoms:
  
  
  • Anticholinergic symptoms: delirium, hyperthermia, ileus, tachycardia, urinary retention, warm and dry skin
  • Cholinergic, muscarinic symptoms: bradycardia, bronchorrhea, meiosis, wheezing
  • Cholinergic, nicotinic symptoms: abdominal pain, fasciculations, hypertension, paresis, tachycardia
  • Opioid symptoms: hypotension, hypothermia, hypoventilation, meiosis, sedation
  • Sympathomimetic symptoms: agitation, diaphoresis, hypertension, hyperthermia, mydriasis, psychosis, seizures, tachycardia
• Certain medications have specific therapies:
  
  
  • Acetaminophen: N-acetylcysteine
  • Benzodiazepines: flumazenil unless contraindicated
  • Beta-blockers: glucagon, calcium gluconate, epinephrine, insulin plus dextrose, sodium bicarbonate
  • Calcium channel antagonists: glucagon, calcium gluconate, epinephrine, insulin euglycemia therapy, or sodium bicarbonate
  • Clonidine: naloxone, atropine, dopamine
  • Opioids: naloxone
  • Salicylates: urine alkalinization, possible hemodialysis
  • Sulfonylureas: dextrose, octreotide, glucagon
  • Tricyclic antidepressants: benzodiazepines, sodium bicarbonate, and dopamine or norepinephrine
• Children have different treatment doses and are affected by smaller ingestions.
• Disposition to intensive care unit, tertiary care facility, home, or psychiatric care depends on patient's stability, medication half-life, amount ingested, formulation, persistent signs and symptoms, home situation, suicidal attempt, and substance abuse.

Clinical Implications

• The initial evaluation of acute medication poisoning includes assessment of airway, breathing, and circulation; thorough history; and determination of the presence of transdermal patches.
• In most cases of medication poisoning, the gastrointestinal decontamination modality of choice is single-dose activated charcoal, which can be given up to 1 hour after ingestion. Ipecac syrup use is not indicated.

CME/CE Test

Questions answered incorrectly will be highlighted.

In a patient who is suspected of ingesting a toxic amount of medication, assessment of which of the following is most likely to be useful in the initial evaluation of acute poisoning?

Skin

Airway

History

Circulation

All of the above

A 40-year-old patient presenting in the emergency department for medication poisoning needs gastrointestinal decontamination. Which of the following forms is most likely to be recommended?

Ipecac syrup

Activated charcoal

Gastric lavage

Whole-bowel irrigation

All of the above