The Spectrum of Alcohol Use: Epidemiology, Diagnosis, and Treatment.

In the United States, alcohol is the most common substance used and the spectrum of unhealthy alcohol use is highly prevalent. Complications of unhealthy alcohol use affect nearly every organ system. One of the most frequent and potentially life-threatening of these complications is alcohol withdrawal syndrome for which benzodiazepines remain first-line therapy. Pharmacologic treatment of alcohol use disorder, the most severe form of unhealthy alcohol use, is underutilized despite the availability of multiple effective medications. Although behavioral therapies are an important component of treatment, they are overemphasized at the expense of pharmacotherapy.

Specialist alcohol inpatient treatment admissions and non-specialist hospital admissions for alcohol withdrawal in England: an inverse relationship.

AIMS: We assessed the relationship between specialist and non-specialist admissions for alcohol withdrawal since the introduction of the UK government Health and Social Care Act in 2012. METHODS: Using publicly available national data sets from 2009 to 2019, we compared the number of alcohol withdrawal admissions and estimated costs in specialist and non-specialist treatment settings. RESULTS: A significant negative correlation providing strong evidence of an association was observed between the fall in specialist and rise in non-specialist admissions. Significant cost reductions within specialist services were displaced to non-specialist settings. CONCLUSIONS: The shift in demand from specialist to non-specialist alcohol admissions due to policy changes in England should be reversed by specialist workforce investment to improve outcomes. In the meantime, non-specialist services and staff must be resourced and equipped to meet the complex needs of these service users.

Assessment of Amphetamine Withdrawal Symptoms of Lisdexamfetamine Dimesylate Treatment for Adults With Binge-Eating Disorder.

OBJECTIVE: To determine whether physical dependence developed during lisdexamfetamine dimesylate treatment, as evidenced by presence of withdrawal symptoms after treatment cessation in adults with binge-eating disorder (BED) treated for up to 38 weeks. METHODS: Three studies enrolled adults with DSM-IV-TR-defined BED. In two 12-week, randomized, double-blind, placebo-controlled studies conducted from November 2012 to September 2013, participants were treated with placebo or dose-optimized lisdexamfetamine (50 or 70 mg). In a double-blind, placebo-controlled, randomized-withdrawal maintenance-of-efficacy study conducted from January 2014 to April 2015, participants categorized as responders after 12 weeks of open-label lisdexamfetamine (50 or 70 mg) were randomized to continued lisdexamfetamine or placebo for 26 weeks. The Amphetamine Cessation Symptom Assessment (ACSA), a 16-item self-report instrument (total score: 0-64), assessed withdrawal experiences. Mean ± SD ACSA scores and medians are presented for study completers. RESULTS: In the short-term efficacy studies, mean ± SD ACSA aggregate scores for placebo and lisdexamfetamine (pooled data) were 7.0 ± 7.60 (n = 275) and 4.9 ± 6.41 (n = 271), respectively, on the day of the last dose at week 12/early termination (ET) and 4.8 ± 6.82 (n = 234) and 5.5 ± 7.50 (n = 221) on day 7 after the last dose. In the maintenance-of-efficacy study, mean ± SD ACSA aggregate scores for placebo and lisdexamfetamine were 4.8 ± 6.67 (n = 44) and 4.7 ± 7.78 (n = 85) on the day of the last dose at week 38/ET and 3.9 ± 5.75 (n = 37) and 5.2 ± 7.93 (n = 71) on day 7 after the last dose. CONCLUSIONS: Study results suggest that abrupt lisdexamfetamine termination was not associated with amphetamine withdrawal symptoms at the exposure durations and therapeutic doses analyzed. TRIAL REGISTRATION: Clinicaltrials.gov identifiers: NCT01718483, NCT01718509, and NCT02009163.

Pharmacologic and clinical assessment of kratom: An update.

PURPOSE: This article presents updated information on kratom (Mitragyna speciosa), a natural opioid with stimulant properties that is currently sold in the United States without a prescription. SUMMARY: Kratom exerts opioid and alpha-2 agonistic effects, as well as anti-inflammatory and mild stimulant effects. Respiratory depression has not been commonly reported, but kratom does cause a host of adverse effects. While kratom may have a role in patients who are in chronic pain or dependent on opioid painkillers or heroin, this needs to be established in clinical trials. Kratom may have drug interactions as both a cytochrome P-450 system substrate and inhibitor. Kratom does not appear in normal drug screens and, especially when ingested with other substances of abuse, may not be recognized as an agent of harm. There are numerous cases of death in kratom users, but many involved polypharmaceutical ingestions. There are assessments where people have been unable to stop using kratom therapy and withdrawal signs/symptoms occurred in patients or their newborn babies after kratom cessation. Both banning and failure to ban kratom places people at risk; a middle-ground alternative, placing it behind the pharmacy counter, might be useful. CONCLUSION: Kratom has a unique pharmacologic profile that might offer advantages over other opioids, but its high abuse liability, potential for drug interactions and adverse events, and inadequate research into the balance of benefits to harm are concerning. There is mounting information on the adverse events associated with kratom use and potential treatments that can be useful to clinicians.

Management of opioid use disorder in the USA: present status and future directions.

Opioid use disorder is characterised by the persistent use of opioids despite the adverse consequences of its use. The disorder is associated with a range of mental and general medical comorbid disorders, and with increased mortality. Although genetics are important in opioid use disorder, younger age, male sex, and lower educational attainment level and income, increase the risk of opioid use disorder, as do certain psychiatric disorders (eg, other substance use disorders and mood disorders). The medications for opioid use disorder, which include methadone, buprenorphine, and extended-release naltrexone, significantly improve opioid use disorder outcomes. However, the effectiveness of medications for opioid use disorder is limited by problems at all levels of the care cascade, including diagnosis, entry into treatment, and retention in treatment. There is an urgent need for expanding the use of medications for opioid use disorder, including training of health-care professionals in the treatment and prevention of opioid use disorder, and for development of alternative medications and new models of care to expand capabilities for personalised interventions.

Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment.

BACKGROUND AND OBJECTIVES: The opioid crisis has taken an immense toll in the United States. On average, five lives are lost to an opioid overdose every hour of the day; estimated costs associated with opioid misuse exceed $500 billion annually. Illicit opioid discontinuation is the first step in the treatment of opioid use disorder (OUD), and transition to an opioid agonist may initiate treatment. However, discontinuation to abstinence from either OUD directly or following agonist treatment results in severely distressing opioid withdrawal symptoms (OWS). METHODS: This review evaluated studies on the etiology, burden, and management of OWS. RESULTS: Noradrenergic hyperactivity generates many OWS. These OWS can cause patients to relapse during early opioid discontinuation. While agonist therapies are generally first-line for moderate or severe OUD and reduce OWS, prescribing restrictions can limit their availability. DISCUSSION AND CONCLUSIONS: Non-opioid medications to treat OWS provides a gateway into long-term treatment with naltrexone or psychosocial therapies. For opioid dependent patients without OUD, non-opioid treatments like α-2 adrenergic agonists can facilitate opioid tapering. SCIENTIFIC SIGNIFICANCE: For the millions who are physically dependent on opioids, new treatments for OWS can enhance recovery from OUD and prevent relapse. (© 2019 The Authors. The American Journal on Addictions Published by Wiley Periodicals, Inc.;XX:1-8).

Self-initiated gradual smoking reduction among community correction smokers.

INTRODUCTION: Smoking remains the leading cause of preventable death in the United States. Many smoking cessation guidelines advise smokers to quit precipitately; however, most quit attempts involve a more gradual cessation. Characteristics of individuals who tend to reduce prior to quitting and the effectiveness of pre-quit reduction are not well understood. This study examined individual differences and smoking cessation outcomes between individuals who self-initiated gradual reduction in cigarettes per day (CPD) and those who did not reduce prior to quit date. METHODS: This study is a secondary analysis from a randomized clinical trial of smoking cessation with pharmacotherapy among individuals under community corrections supervision. We compared participants who self-initiated smoking reduction by at least 25% between baseline and the first treatment session (n = 128) to participants who either increased or did not reduce smoking between baseline and the first treatment session (n = 354). RESULTS: African American race, no previous cigar smoking, no previous use of pharmacotherapy for smoking cessation, less withdrawal symptoms at baseline, and older age at first smoking were associated with being a self-initiated gradual reduction in univariate analyses. Individuals who self-initiated gradual reduction also had a had a greater likelihood of achieving at least one quit during the one-year study period as compared to those who did not reduce prior to the intervention. CONCLUSIONS: Individuals who self-initiate gradual reduction differ from those who increase or do not change their smoking prior to a quit date. Gradual reduction also increased success in quitting.

Prevalence of withdrawal symptoms from electronic cigarette cessation: A cross-sectional analysis of the US Population Assessment of Tobacco and Health.

Electronic cigarette use can produce rapid and high levels of nicotine and thus could produce or maintain a physical dependence on nicotine. No experimental and limited observational studies have tested whether cessation of e-cigarettes is associated with withdrawal symptoms. To examine withdrawal from electronic cigarettes and compare it to that from tobacco cigarettes, we searched the US Population Assessment of Tobacco and Health Survey to locate successful and unsuccessful attempts to stop electronic or tobacco cigarettes. We examined electronic cigarette-only users, tobacco cigarette-only users and dual users. A minority of e-cigarette users who stopped/reduced e-cigarettes reported withdrawal symptoms but reported fewer symptoms than tobacco cigarette users who stopped/reduced tobacco cigarettes. E-cigarette withdrawal was not significantly greater in those who tried but were unable to stop e-cigarettes. In dual users, continued tobacco use appeared to reduce e-cigarette withdrawal but the opposite was not true. Given our small sample size and use of retrospective recall, an experimental test of e-cigarette abstinence is needed to better describe the severity of electronic cigarette withdrawal.

Withdrawal Assessment Tool-1 Monitoring in PICU: A Multicenter Study on Iatrogenic Withdrawal Syndrome.

OBJECTIVES: Withdrawal syndrome is an adverse reaction of analgesic and sedative therapy, with a reported occurrence rate between 17% and 57% in critically ill children. Although some factors related to the development of withdrawal syndrome have been identified, there is weak evidence for the effectiveness of preventive and therapeutic strategies. The main aim of this study was to evaluate the frequency of withdrawal syndrome in Italian PICUs, using a validated instrument. We also analyzed differences in patient characteristics, analgesic and sedative treatment, and patients' outcome between patients with and without withdrawal syndrome. DESIGN: Observational multicenter prospective study. SETTING: Eight Italian PICUs belonging to the national PICU network Italian PICU network. PATIENTS: One hundred thirteen patients, less than 18 years old, mechanically ventilated and treated with analgesic and sedative therapy for five or more days. They were admitted in PICU from November 2012 to May 2014. INTERVENTIONS: Symptoms of withdrawal syndrome were monitored with Withdrawal Assessment Tool-1 scale. MEASUREMENTS AND MAIN RESULTS: The occurrence rate of withdrawal syndrome was 64.6%. The following variables were significantly different between the patients who developed withdrawal syndrome and those who did not: type, duration, and cumulative dose of analgesic therapy; duration and cumulative dose of sedative therapy; clinical team judgment about analgesia and sedation's difficulty; and duration of analgesic weaning, mechanical ventilation, and PICU stay. Multivariate logistic regression analysis revealed that patients receiving morphine as their primary analgesic were 83% less likely to develop withdrawal syndrome than those receiving fentanyl or remifentanil. CONCLUSIONS: Withdrawal syndrome was frequent in PICU patients, and patients with withdrawal syndrome had prolonged hospital treatment. We suggest adopting the lowest effective dose of analgesic and sedative drugs and frequent reevaluation of the need for continued use. Further studies are necessary to define common preventive and therapeutic strategies.

Assessment of the appropriateness of naloxone administration to patients receiving long-term opioid therapy.

BACKGROUND: The most dangerous adverse effect of opioids is respiratory depression. Naloxone is used to reverse this, although in patients receiving long-term opioid therapy it can cause acute opioid withdrawal and opioid-refractory pain. OBJECTIVE: To determine if naloxone is appropriately administered to patients receiving long-term opioid therapy. METHODS: This retrospective case series based on chart reviews systematically identified patients over one year in a district general hospital. All patients aged 18 years or older receiving long-term opioid therapy admitted to medicine, surgery or the high dependency unit who were administered naloxone during their admission were included. RESULTS: A total of 1206 patient drug administration records were reviewed. Sixteen patients receiving long-term opioid therapy were administered naloxone. Twelve of these did not have opioid-induced respiratory depression and four did not have respiratory rate and oxygen saturations documented in the medical notes. All naloxone doses administered were higher than those recommended by national guidelines for this patient group. CONCLUSIONS: No patient receiving long-term opioid therapy who was administered naloxone had evidence of respiratory depression. More thorough assessment and documentation are needed. Verbal and physical stimulation as well as oxygenation should be considered prior to naloxone administration; this should be followed by close observation, hydration, renal function tests and opioid dose review.

Assessment of affective and somatic signs of ethanol withdrawal in C57BL/6J mice using a short-term ethanol treatment.

Alcohol is one of the most prevalent addictive substances in the world. Withdrawal symptoms result from abrupt cessation of alcohol consumption in habitual drinkers. The emergence of both affective and physical symptoms produces a state that promotes relapse. Mice provide a preclinical model that could be used to study alcohol dependence and withdrawal while controlling for both genetic and environmental variables. The use of a liquid ethanol diet offers a reliable method for the induction of alcohol dependence in mice, but this approach is impractical when conducting high-throughput pharmacological screens or when comparing multiple strains of genetically engineered mice. The goal of this study was to compare withdrawal-associated behaviors in mice chronically treated with a liquid ethanol diet vs. mice treated with a short-term ethanol treatment that consisted of daily ethanol injections containing the alcohol dehydrogenase inhibitor, 4-methylpyrazole. Twenty-four hours after ethanol treatment, mice were tested in the open field arena, the elevated plus maze, the marble burying test, or for changes in somatic signs during spontaneous ethanol withdrawal. Anxiety-like and compulsive-like behaviors, as well as physical signs, were all significantly elevated in mice undergoing withdrawal, regardless of the route of ethanol administration. Therefore, a short-term ethanol treatment can be utilized as a screening tool for testing genetic and pharmacological agents before investing in a more time-consuming ethanol treatment.

Withdrawal assessment following subchronic oral ketamine administration in Cynomolgus macaques.

Recently there is increased regulatory interest in the assessment of physical dependence and withdrawal as part of the safety assessment for novel therapeutic entities. Choosing appropriate and sensitive parameters to detect withdrawal syndromes, and relevant positive control comparator drugs that can be administered in the same manner as the test agent, are critical study design elements. Pilot studies to determine the effects of oral ketamine in cynomolgus monkeys during, and following cessation of treatment, were explored. Detailed behavioral observations (both remote and interactive), food consumption, and body weight and temperature, were assessed during the dose-ranging, repeat dose (5 or 14 days), and withdrawal phases (3 or 5 days). Doses explored during dose-ranging included 20, 40, 100, or 200 mg/kg ketamine; subsequent withdrawal assessments were conducted following repeat dosing of 150 mg/kg. In the 14-day dosing study, exposure to ketamine and norketamine was assessed following 8 days of dosing. Administration of 150 mg/kg ketamine produced decreased activity, loss of balance, ataxia, hunched posture, nystagmus, lateral recumbence, and changes in alertness levels during dosing phases. When ketamine was withdrawn, increased reactivity, increased activity, and stereotypic behaviors were demonstrated that were absent during baseline or the dosing phase of the studies.

Prescription opioid use among university students: assessment of post-cue exposure craving.

Despite the increasing number of prescriptions written to adolescents and young adults for opioid analgesics, the rise in non-medical use of such drugs among university students, and the potential role of craving in the misuse of opioids, there have been no published studies assessing craving for prescription opioids in this population. Therefore, the current study was designed to assess the impact of prescription opioid-related cue exposure on craving in university students. Students (n=277) recruited from a large university in the Midwestern United States were randomly assigned to two conditions to test the impact of cue exposure to either prescription opioid-related stimuli or control stimuli. Relative to the control condition, prescription opioid-related cue exposure significantly increased overall craving, desire and intention to use prescription opioids, relief from negative states by using prescription opioids, and perceived control over prescription opioid use. In addition, when assessing correlates of post-cue exposure craving, negative mood and procurement of prescription opioids from non-medical sources were the only measured variables that were significantly associated with overall craving and/or any of the craving measure's subscales. Craving may be important aspect of prescription opioid use among university students. Future research assessing craving as a function of non-medical user subtype is warranted.

Predictors of success for smoking cessation at the workplace: a longitudinal study.

BACKGROUND: The effectiveness of worksite interventions to reduce smoking is debatable. OBJECTIVES: A comprehensive smoking cessation intervention was implemented in a community of more than 17,000 employees at three different health care companies. The primary endpoint was abstinence at 24 months (self-reported and confirmed by exhaled carbon monoxide ≤ 6 parts per million). Predictors of long-term abstinence were analysed by multivariable regression analysis. METHODS: The study was designed as an investigator-initiated and investigator-driven, open, multicentre, cohort study; 887 smokers were enrolled in the programme. The intervention included intensive individual counselling as well as nicotine replacement and/or bupropion according to individual preferences. Re-interventions for relapse were offered during the 24-month follow-up. RESULTS: The abstinence rate was 37% at 24 months and did not differ among the various medication groups (p > 0.05 for all). Predictors of successful cessation were higher age (odds ratio, OR 1.47, 95% confidence interval, CI 1.08-2.00, p < 0.01), breathlessness on exertion (OR 2.26, 95% CI 1.1-4.9, p = 0.03), and a higher educational level (OR 1.81, 95% CI 1.06-3.09, p = 0.03). Higher Fagerström (OR 0.76, 95% CI 0.59-0.97, p < 0.01) and craving scores (OR 0.75, 95% CI 0.63-0.89, p < 0.01), chronic sputum production (OR 0.52, 95% CI 0.31-0.87, p = 0.01) and use of antidepressants (OR 0.54, 95% CI 0.32-0.91, p = 0.02) were associated with ongoing smoking. CONCLUSION: A comprehensive smoking cessation intervention at the workplace achieves high, stable, long-term abstinence rates. Elderly, well-educated employees with breathlessness on exertion have higher odds of quitting smoking. In contrast, those with high physical dependency and more intense craving, and those reporting use of antidepressant medication or sputum production have poorer chances to quit.

Predictors of quit attempts and successful quit attempts in a nationally representative sample of smokers.

Although most current smokers report that they would like to quit, most quit attempts fail suggesting that predictors of quitting attempts may differ from those of successful attempts. We examined sociodemographic and clinical predictors of quit attempts and successful quit attempts in a nationally representative sample of US adults. Data was collected in 2001-2002 (Wave 1) and 2004-2005 (Wave 2). Almost 40% of individuals who had not previously attempted to quit, tried to quit over the next three years; only 4.6% of those who tried had succeeded at the time of the evaluation. Hispanics, Asians, individuals with high income, and those with college education were less likely to attempt to quit, whereas those with daily nicotine use, younger age at first use and most symptoms of dependence were more likely to do so. Having an educational level below high school and older age at first nicotine use were predictors of successful quitting. Despite relatively high rates of quit attempts, rates of success are extremely low, indicating a gap between the public health need of decreasing tobacco use, and existing means to achieve it. Although there is a need to encourage people to quit tobacco, there may be an equally large need to develop more effective interventions that increase the rate of successful quit attempts.

Reasons for and time to discontinuation of rimonabant therapy: a modified prescription-event monitoring study.

BACKGROUND: Early treatment discontinuation will have a negative effect on a drug's benefit-risk profile if discontinuation occurs earlier in time than the positive effects of treatment. This non-persistence of therapy has been associated with an increased risk of adverse health outcomes. OBJECTIVE: The aim of this study was to explore relationships between patient characteristics and reasons for and time to discontinuation of rimonabant therapy, focusing on psychiatric events, because these were the main safety concerns for rimonabant. METHODS: A modified prescription-event monitoring (M-PEM) study was conducted for rimonabant. Descriptive statistics were used to describe the patient population. Rate ratios with 95% confidence intervals (CIs) were calculated to explore associations between patient characteristics and selected categories of reasons for stopping (RfS). Median times to discontinuation were compared using the Mann-Whitney U test. RESULTS: The cohort comprised 10,011 users of rimonabant, three of which were excluded from this analysis because of missing age or sex. A total of 7204 patients (72.0%) stopped using rimonabant (median observation time 323 days, interquartile range: 279-371 days). In addition, patients with a history of psychiatric illness were more likely to discontinue rimonabant therapy early for all reasons, but most pronounced due to psychiatric events (rate ratio 1.79; 95% CI 1.54, 2.09) than those without a history of psychiatric illness. In contrast, the rates of discontinuation due to lack of effectiveness, any clinical events and psychiatric events in patients with cardiovascular disease, type 2 diabetes mellitus, dyslipidaemia or hypertension tended to be lower (not all being significant) than those without. For patients who discontinued treatment due to lack of effectiveness, the median time to discontinuation was significantly shorter for patients with a history of psychiatric illness, compared with patients without a history of psychiatric illness (86 vs 97 days, p = 0.03). For patients discontinuing treatment due to psychiatric events, the difference in median time to discontinuation was also 11 days (64 vs 75 days, p = 0.38), although not statistically significant. For patients stopping due to any clinical event, median time to discontinuation was comparable for patients with and without a history of psychiatric illness (61 vs 63 days, p = 0.90). CONCLUSIONS: In this study, reasons for and time to discontinuation were associated with patient characteristics such as medical history. Patients discontinued treatment because of psychiatric events early after starting. In general, identification and characterization of early discontinuers, and increasing the understanding of reasons for stopping, may help healthcare professionals to develop targeted interventions to further improve treatment compliance, thereby optimizing treatment benefits and drug safety.

Science, rhetoric and the causality of adverse events.

This paper outlines aspects of the interface between law and science in the domain of treatment induced injury, using examples drawn from litigation on SSRIs. In the face of claims that randomized controlled trials provide uniquely appropriate evidence and that there should be a statistically significant doubling of the risks on treatment, the examples used demonstrate that the methods of assessing the possibility of causal links between treatment and injuries must necessarily be tailored to both the injury and the treatment.

Prospective assessment of cannabis withdrawal in adolescents with cannabis dependence: a pilot study.

OBJECTIVE: To prospectively identify and assess withdrawal symptoms in adolescents with cannabis dependence. METHOD: Twenty-one adolescents ages 13 to 19 years voluntarily entering residential and day/outpatient substance abuse programs, with cannabis dependence as their only current substance of dependence, were assessed using the Teen-Addiction Severity Index, Substance Use Survey, Cannabis Withdrawal Scale, and the Structured Clinical Interview for DSM-IV Childhood Diagnoses Substance Use Disorders Module. Weekly assessments continued for 4 weeks. Thirteen youths attained a minimum of 2 weeks of abstinence. RESULTS: Cannabis withdrawal symptoms were present in adolescents. Cannabis withdrawal was greatest in the first 2 weeks of abstinence with evidence that it continued well into week 3. Most withdrawal symptoms were endorsed with a high degree of frequency. Those symptoms endorsed with the greatest severity were restlessness, appetite change, and thoughts of and cravings for cannabis, with the highest ratings occurring in week 1. Over the course of the study, participants reported fewer symptoms with decreasing levels of severity. Youth ratings of overall severity of withdrawal were significantly and positively correlated with withdrawal symptoms of irritability (r = 0.56), depression (r = 0.56), twitches and shakes (r = 0.57), perspiring (r = 0.57), thoughts of (r = 0.86), and cravings for (r = 0.69) cannabis. CONCLUSIONS: Findings support the presence of clinically significant cannabis withdrawal symptoms in adolescents with cannabis dependence seeking substance abuse treatment. This study also provides supporting evidence suggesting a vulnerability of adolescents to physiological cannabis dependence. The study supports the addition of cannabis withdrawal as a distinct entity for inclusion in DSM-V.

Postoperative medical complications--not microsurgical complications--negatively influence the morbidity, mortality, and true costs after microsurgical reconstruction for head and neck cancer.

BACKGROUND: Immediate reconstruction of composite head and neck defects using free tissue transfer is an accepted treatment standard. There remains, however, ongoing debate on whether the costs associated with this reconstructive approach merit its selection, especially considering poor patient prognoses and the high cost of care. METHODS: A retrospective review of the last 100 consecutive patients undergoing microsurgical reconstruction for head and neck cancer by the two senior surgeons was performed to determine whether microsurgical complications or postoperative medical complications had the more profound influence on morbidity and mortality outcomes and the true costs of these reconstructions. RESULTS: Two patients required re-exploration of the microsurgical anastomoses, for a re-exploration rate of 2 percent, and one flap failed, for a flap success rate of 99 percent. The major surgical complication rate requiring a second operative procedure was 6 percent. Sixteen percent had minor surgical complications related to the donor site. Major medical complications, defined as a significant risk to the patient's life, occurred in 5 percent of the patients, but there was a 37 percent incidence of "minor" medical complications primarily caused by pulmonary problems and alcohol withdrawal. Postsurgical complications almost doubled the average hospital stay from 13.5 days for those patients without complications to 24 days for patients with complications. Thirty-six percent of the true cost of microsurgical reconstruction of head and neck cancer was due to the intensive care unit and hospital room costs, and 24 percent was due to operating room costs. Postsurgical complications resulted in a 70.7 percent increase in true costs, reflecting a prolonged stay in the intensive care unit and not an increase in operating room costs or regular hospital room costs. CONCLUSION: Postoperative medical complications in these elderly, debilitated patients related to pulmonary problems and alcohol withdrawal were statistically far more important in negatively affecting the outcomes and true costs of microsurgical reconstruction.