Paramedic rapid sequence intubation in patients with non-traumatic coma.

INTRODUCTION: Pre-hospital intubation by paramedics is widely used in comatose patients prior to transportation to hospital, but the optimal technique for intubation is uncertain. One approach is paramedic rapid sequence intubation (RSI), which may improve outcomes in adult patients with traumatic brain injury. However, many patients present to emergency medical services with coma of non-traumatic cause and the role of paramedic RSI in these patients remains uncertain. METHODS: The electronic Victorian Ambulance Clinical Information System was searched for the term 'suxamethonium' between 2008 and 2011. We reviewed the patient care records and included patients with suspected non-traumatic coma who were treated and transported by road-based paramedics. Demographics, intubation conditions, vital signs (before and after drug administration) and complications were recorded. Younger patients (<60 years) were compared with older patients. RESULTS: There were 1152 paramedic RSI attempts of which 551 were for non-traumatic coma. The success rate for intubation was 97.5%. There was a significant drop in blood pressure in younger patients (<60 years) with the mean systolic blood pressure decreasing by 16 mm Hg (95% CI 11 to 21). In older patients, the systolic blood pressure also decreased significantly by 20 mm Hg (95% CI 17 to 24). Four patients suffered brief cardiac arrest during pre-hospital care, all of whom were successfully resuscitated and transported to hospital. CONCLUSIONS: Paramedic RSI in patients with non-traumatic coma has a high procedural success rate. Further studies are required to determine whether this procedure improves outcomes.

Paediatric traumatic out-of-hospital cardiac arrests in Melbourne, Australia.

INTRODUCTION: Many consider attempted resuscitation for traumatic out-of-hospital cardiac arrest (OHCA) futile. This study aims to describe the characteristics and profile of paediatric traumatic OHCA. METHODS: The Victorian Ambulance Cardiac Arrest Registry (VACAR) was used to identify all trauma related cases of OHCA in patients aged less than 16 years of age. Cases were linked with their coronial findings. RESULTS: Between 2000 and 2009, EMS attended 33,722 OHCAs including 2187 adult traumatic OHCAs. There were 538 (1.6%) OHCAs in children less than 16 years of age of which n=64 were due to trauma. The median age (IQR) of paediatric traumatic OHCA was 7 (4.5-13) years and 44 were male (69%). Bystander CPR was performed in 22 cases (34.4%). The first recorded rhythm by EMS was asystole seen in 42 (66%), PEA in 14 (22%) cases and VF in 2 cases (3%). Cardiac output was present in 7 (11%) cases who subsequently had an EMS witnessed OHCA. EMS attempted resuscitation in 35 (55%) patients of whom 7 (20%) achieved ROSC and were transported, and 1 (3%) survived to hospital discharge with severe neurological sequelae; 14(40%) were transported with CPR of whom none survived. Coronial cause of death was multiple injuries in 35%, head injury in 33%, head and neck injury in 10%, chest injuries in 10% and other causes (12%). CONCLUSIONS: Traumatic aetiology of OHCA when compared to the incidence of adult traumatic OHCAs is uncommon. Resuscitation efforts are seldom effective and associated with poor neurological outcome.

Resuscitation of out-of-hospital cardiac arrests in residential aged care facilities in Melbourne, Australia.

INTRODUCTION: CPR in patients in residential aged care facilities (RACF) deserves careful consideration. We examined the characteristics, management and outcomes of out-of-hospital cardiac arrest (OHCA) in RACF patients in Melbourne, Australia. METHODS: The Victorian Ambulance Cardiac Arrest Registry (VACAR) was searched for all OHCAs occurring in RACFs in Melbourne. The characteristics and outcomes were compared to non-RACF patients in the VACAR. RESULTS: Between 2000 and 2009 there were 30,006 OHCAs, 2350 (7.8%) occurring in a RACF. A shockable rhythm was present in 179 (7.6%) patients on arrival of paramedics of whom bystander CPR had been performed in 118 (66%); 173 (97%) received an EMS attempted resuscitation. ROSC was achieved in 71 (41%) patients and 15 (8.7%) patients survived to leave hospital. Non shockable rhythm was present in 2171 patients (92%) of whom 804 (37%) had an attempted resuscitation by paramedics. ROSC was achieved in 176 patients (22%) and 10 patients (1.2%) were discharged alive. Survival from OHCA occurring in a RACF was less than survival in those aged >70 years of age who suffered OHCA in their own homes (1.8% vs. 4.7%, p=0.001). On multivariable analysis, witnessed OHCA (OR 3.0, 95% CI 2.4-3.7) and the presence of bystander CPR (OR 4.6, 95% CI 3.7-5.8) was associated with the paramedic decision to resuscitate. CONCLUSION: Resuscitation of patients in RACF is not futile. However, informed decisions concerning resuscitation status should be made by patients and their families on entry to a RACF. Where it is appropriate to perform resuscitation, outcomes may be improved by the provision of BLS training and possibly AED equipment to RACF staff.

Out-of-hospital cardiac arrests in young adults in Melbourne, Australia-adding coronial data to a cardiac arrest registry.

AIM: We aim to describe the coronial findings of young adults where the out-of-hospital cardiac arrest (OHCA) aetiology was 'presumed cardiac'. METHODS: Presumed cardiac aetiology OHCAs occurring in young adults aged 16-39 years were identified using the Victorian Ambulance Cardiac Arrest Registry (VACAR) and available coronial findings reviewed. RESULTS: We identified 841 young adult OHCAs where the Utstein aetiology was 'presumed cardiac'. Of these 740 died and 572 (77%) OHCAs were matched to coroner's findings. On review of the coroner's cause of death, 230 (40.2%) had a 'confirmed cardiac' aetiology, 221 (38.6%) were proven 'non-cardiac', 97 (17%) were inconclusive and 24 (4.2%) cases remained 'open'. 'Confirmed cardiac' causes of OHCA were ischemic heart disease (n=126, 55%), cardiomegaly (n=26, 11.3%), cardiomyopathy (n=25, 11%), congenital heart disease (n=15, 6.5%), cardiac tamponade due to dissecting thoracic aorta aneurysm (n=10, 4.3%), myocarditis (n=8, 3.5%), arrhythmia (n=7, 3%), others (n=13, 5.7%). 'Non-cardiac' causes of OHCA were epilepsy/sudden unexplained death in epilepsy (SUDEP) (n=56, 25%), pulmonary embolism (n=29, 13%), subarachnoid haemorrhage (n=17, 7.7%), other intracranial bleed (n=7, 3.2%), pneumonia (n=17, 7.7%), DKA (n=16, 7.2%), other complications of diabetes mellitus (n=8, 3.6%), complications of obesity (n=9, 4%), haemorrhage (n=12, 5.4%), sepsis (n=8, 3.6%), peritonitis (n=6, 2.7%), aspiration (n=6, 2.7%), renal failure (n=5, 2.3%), asthma (n=5, 2.3%), complications of anorexia (n=3) and alcohol abuse (n=2), thyrotoxicosis (n=2), meningitis (n=1) and others (n=12). Compared with coroner's diagnosed 'non-cardiac' OHCAs, 'confirmed cardiac' were more likely to be witnessed (41% vs 23%, p≤0.01), receive bystander CPR (35% vs 20%, p≤0.001), have a shockable rhythm (27% vs 6.3%, p<0.001) and have EMS attempted resuscitation (62% vs 44%, p<0.001). DISCUSSION: Linking OHCA registries with coronial databases for aetiology of the arrest will improve the quality of the data and should be considered by all OHCA registries, particularly for young adult OHCA.

Cardiac arrest outcomes before and after the 2005 resuscitation guidelines implementation: evidence of improvement?

BACKGROUND: Previous studies have reported improvements in out-of-hospital cardiac arrest (OHCA) outcomes with the introduction of the 2005 cardiopulmonary resuscitation guidelines however they have not adjusted for underlying trends in OHCA survival. We compare outcomes before and after the 2005 guideline changes adjusting for underlying trends in OHCA survival. METHODS: The Victorian Ambulance Cardiac Arrest Registry (VACAR) was searched for adult (≥16 years) OHCA of presumed cardiac aetiology, unwitnessed by paramedics with attempted resuscitation. Outcomes for OHCA occurring between 2003 and 2005 were compared with 2007-2009. Segmented regression analysis of interrupted time series data was performed, adjusting for known predictors, to examine changes in survival to hospital and survival to hospital discharge. RESULTS: For the pre- and post- guideline periods there were 3115 and 3248 OHCAs, respectively. Asystole increased as presenting rhythm (33-43%, p<0.001) as did median EMS response times (7.1-7.8 min, p<0.001) over the two periods. VF/VT arrests decreased (40-35.5%, p=0.001) as did bystander witnessed arrests (63-59%, p=0.002). On univariate analysis survival to hospital discharge improved between the two periods (9.4-11.8%, p=0.002) due to improved outcomes in VF/VT (19-28%, p<0.001). Segmented regression analysis of interrupted time series data showed improvement in the rate of survival to get to hospital for shockable and non-shockable rhythms [OR (95% CI)=1.54 (1.10-2.15, p=0.01) and 1.45 (1.10-2.00, p=0.02), respectively] following implementation of the guidelines however survival to hospital discharge did not improve [OR=1.07 (0.70-1.62, p=0.70) and 1.40 (0.69-2.85, p=0.40), respectively]. CONCLUSIONS: OHCA outcomes have improved since introduction of the 2005 CPR guidelines, but multivariable segmented regression analysis adjusting for pre-existing trends in survival suggests that this improvement may not be due to implementation of the 2005 resuscitation guidelines.

Out-of-hospital cardiac arrests in young adults in Melbourne, Australia.

BACKGROUND: Characteristics and outcomes of out-of-hospital cardiac arrest (OHCA) in young adults are not well described in Australia. METHODS: A 10-year retrospective case review of all OHCA in young adults (aged 16-39) and not witnessed by EMS, was performed using data from the Victorian Ambulance Cardiac Arrest Registry (VACAR). RESULTS: Between 2000 and 2009 there were 30,006 adult cardiac arrests of which 3912 (13%) were in this age group. The median (IQR) age was 30 (25-35) years for both sexes with a 3:1 male to female ratio. Overdose was the most common precipitant (33.5%) followed by presumed cardiac (20%). Bystander CPR occurred in 21.2%, EMS median response time was 7 min and resuscitation was attempted in 36% of OHCAs. The presenting rhythm was asystole in 84.6%, PEA in 8.8% and VF/VT in 6.6%. Survival to hospital discharge, for all cause OHCA where resuscitation was attempted, was similar for young adult and older adults (8.8% vs 8.4%, p=0.2). However, for presumed cardiac aetiology OHCA, young adults had a greater proportion of survivors (14.8% vs 9.0%, p<0.001). Cardiac arrest with shockable rhythm (VF/pulseless VT) had a survival rate of 31.2% for young adults compared to 18.5% for older adults (p<0.001). CONCLUSION: Survival to hospital discharge rates from OHCA due to a 'presumed cardiac' precipitant in young adults is much better than older adults, however, all cause OHCA survival is similar. Multi agency novel upstream preventive strategies aimed at tackling drug overdose may reduce this aetiology of OHCA and save lives.

Paediatric hanging associated out of hospital cardiac arrest in Melbourne, Australia: characteristics and outcomes.

INTRODUCTION: Hanging is a rare but devastating cause of out of hospital cardiac arrest (OHCA). The characteristics and outcomes of hanging associated OHCA in the paediatric age group are described. METHODS: The Victorian Ambulance Cardiac Arrest Registry was searched for patients aged less than 18 years where the precipitant cause of OHCA was hanging. Results were cross checked with the coronial database. RESULTS: During the years 2000-2009, there were 680 paediatric cardiac arrests of which 53 (7.8%) were precipitated by hanging with an incidence of 4.4 per million paediatric patients (<18 years) per year. Median age was 16 (IQR 14-17) years and 58.5% were males. Five were unintentional hangings; median age 3 (IQR 2-4) years. The youngest deliberate hanging associated OHCA was aged 10 years. Most hangings occurred in a house (85%) and bystander cardiopulmonary resuscitation (CPR) was performed in 30%. Asystole was the most common initial cardiac arrest rhythm seen in 50 cases (94%) while three patients had pulseless electrical activity. The emergency medical services (EMS) attempted resuscitation in 18 patients (34%), inserting an endotracheal tube in 13 patients. The majority (n=41) were not transported; seven patients were transported with return of spontaneous circulation (ROSC) and five patients were transported with ongoing CPR. Victims who had bystander CPR were more likely to have EMS attempted resuscitation (p<0.001). Only patients who had received bystander CPR achieved ROSC (p<0.001). Three patients survived to hospital discharge; two survivors suffered severe neurological injury (Cerebral Performance Category Scale 3-4). CONCLUSION: Non-intentional hanging is rare but deliberate hanging with suicidal intent represents a significant proportion of OHCAs in patients under 18 years of age. A focus on prevention is key, as outcomes are poor, with survivors likely to suffer a severe neurological insult.

Out-of-hospital cardiac arrests in the older age groups in Melbourne, Australia.

BACKGROUND: Controversy exists around CPR in the elderly. The characteristics and outcomes of out-of-hospital cardiac arrest (OHCA) in this age group were studied in Melbourne, Australia. METHODS: The Victorian Ambulance Cardiac Arrest Registry (VACAR) was searched for all OHCAs not witnessed by Emergency Medical Services (EMS) occurring in those aged 65 years and older. RESULTS: Between 2000 and 2009 there were 30,006 OHCAs of which 9703 (32%) were in people 65-79 years of age, 6430 (21%) in octogenarians, 1530 (5%) in nonagenarian and 40 (0.1%) in centenarians. Rates of attempted resuscitation decreased with advancing age: 48% for those aged 65-79 years, 39% for octogenarians, 31% for nonagenarians and 17% for centenarians. Similarly rates of survival to hospital discharge decreased with age: 8% for those aged 65-79 years, 4% for octogenarians, 2% for nonagenarians; for 65-79 year olds, octogenarians and nonagenarians survival if in VF/VT was - 17%, 10% and 4%; asystole - 1%, 1% and 0.5%; and PEA - 6%, 3% and 3%, respectively. Multivariable logistic regression shows that between 2000 and 2009 rates of transportation with return of spontaneous circulation have improved for both shockable and non-shockable rhythms [OR 95% CI 1.07(1.04-1.10) and 1.16(1.12-1.20), respectively] but survival to hospital discharge has improved in the shockable rhythm group only [OR 1.12(1.07-1.16)]. CONCLUSION: Outcomes for OHCA with shockable rhythm have improved over the last 10 years for people aged 65 years and over. Quality of life studies should be performed to help inform the community and EMS on appropriate resuscitative efforts.

Epidemiology of paediatric out-of-hospital cardiac arrest in Melbourne, Australia.

BACKGROUND: Previous studies of paediatric cardiac arrest have reported a low survival rate but there is limited data from Australia. We sought to determine the characteristics and outcomes of paediatric out-of-hospital cardiac arrest in Melbourne, Australia. METHODS: Between October 1999 and June 2007, all cases of out-of-hospital cardiac arrest attended by emergency medical services in Melbourne, Australia were entered into a database (the Victorian Ambulance Cardiac Arrest Registry). Data on patients aged less than 16 years in cardiac arrest on arrival of ambulance paramedics was analysed. RESULTS: There were 209 children in cardiac arrest on arrival of paramedics during the study period. Of these, resuscitation was not attempted in 16 children due to signs of definite death. Of the 193 children who had attempted resuscitation, 143 (74%) had an initial cardiac rhythm of asystole, 36 (18%) were in pulseless electrical activity and 14 (7%) were in ventricular fibrillation. There were 49 patients (25%) with return of spontaneous circulation at arrival to hospital of whom 14 (7%) survived to hospital discharge. Of 138 patients without return of a circulation, 120 were transported to hospital with continuing resuscitation and one survived (0.9%). Survival was higher in patients with an initial cardiac rhythm of ventricular fibrillation (5/14; 35%) compared with other rhythms (10/179; 4%), OR 9.38, 95% CI 2.64-33.2. CONCLUSIONS: Overall, 7.7% of paediatric patients with out-of-hospital cardiac arrest survive to leave hospital. Increased survival was seen if the initial cardiac rhythm was ventricular fibrillation. Survival was very rare (<1%) unless there was return of spontaneous circulation prior to hospital arrival.

Diabetes mellitus affects response to neoadjuvant chemoradiotherapy in the management of rectal cancer.

INTRODUCTION: Although diabetic patients with rectal cancer have poorer outcomes than their nondiabetic counterparts, few studies have looked at diabetics' response to therapy as an explanation for this disparity. This study compares the neoadjuvant chemoradiotherapy (CRT) response in diabetic and nondiabetic patients with locally advanced rectal cancers. METHODS: This is a single-institution, retrospective review of rectal cancer patients who received CRT followed by resection from 1995 to 2006. Pretreatment tumor-node-metastasis (TNM) staging was determined using endorectal ultrasound, computed tomography (CT) scan, and magnetic resonance imaging (MRI); post-treatment staging was determined by pathological review. RESULTS: 110 patients were included; seventeen had diabetes and 93 were nondiabetics. Pretreatment staging was similar in both groups. Sixteen of the diabetics (94%) completed CRT compared to 92% (86/93) of the nondiabetics. Tumor downstaging rates were similar in the two groups (53% in diabetics, 52% in nondiabetics). Nondiabetic patients had a higher rate of nodal downstaging although not statistically significant (67% versus 27%, P = 0.80). While none of the diabetics patients achieved a pathologic complete response (pCR), 23% (21/93) of the nondiabetics did (P = 0.039). Local progression rates were higher in the diabetic group (24% versus 5%, P = 0.046). CONCLUSION: Our study shows that neoadjuvant chemoradiotherapy in rectal cancer is less effective in diabetic patients than in nondiabetics. While minimal differences are found in the rate of downstaging, the rate of achieving a complete pathologic response was significantly higher in nondiabetic patients, and in fact was not seen in any of our diabetic patients. This may explain the poorer outcomes seen in diabetic patients with rectal cancer.

Hypothermia improves outcome from cardiac arrest.

Out-of-hospital cardiac arrest is common and patients who are initially resuscitated by ambulance officers and transported to hospital are usually admitted to the intensive care unit (ICU). In the past, the treatment in the ICU consisted of supportive care only, and most patients remained unconscious due to the severe anoxic neurological injury. It was this neurological injury rather than cardiac complications that caused the high rate of morbidity and mortality. However, in the early 1990's, a series of animal experiments demonstrated convincingly that mild hypothermia induced after return of spontaneous circulation and maintained for several hours dramatically reduced the severity of the anoxic neurological injury. In the mid-1990's, preliminary human studies suggested that mild hypothermia could be induced and maintained in post-cardiac arrest patients without an increase in the rate of cardiac or other complications. In the late 1990's, two prospective, randomised, controlled trials were conducted and the results confirmed the animal data that mild hypothermia induced after resuscitation and maintained for 12 - 24 hours dramatically improved neurological and overall outcomes. On the basis of these studies, mild hypothermia was endorsed in 2003 by the International Liaison Committee on Resuscitation as a recommended treatment for comatose patients with an initial cardiac rhythm of ventricular fibrillation. However, the application of this therapy into routine clinical critical care practice has been slow. The reasons for this are uncertain, but may relate to the relative complexity of the treatment, unfamiliarity with the pathophysiology of hypothermia, lack of clear protocols and/or uncertainty of benefit in particular patients. Therefore, recent research in this area has focused on the development of feasible, inexpensive techniques for the early, rapid induction of mild hypothermia after cardiac arrest. Currently, the most promising strategy is a rapid infusion of large-volume (40 mL/kg) ice cold intravenous fluid. Also, newer automated surface cooling/warming devices have been developed which allow tight control of body temperature in the ICU. On the other hand, a number of questions remain. The benefit of hypothermia in non-ventricular fibrillation cardiac arrest remains uncertain. Also, the best timing of induction and the duration of hypothermia after cardiac arrest are uncertain. Clinical trials are currently underway to assess these issues.

Chemoradiation for locally advanced squamous cell carcinoma of the head and neck for organ preservation and palliation.

OBJECTIVES: To measure the efficacy and toxic effects of our chemoradiotherapy regimen by means of response and survival in patients with advanced squamous cell carcinoma of the head and neck (HNSCC) for organ preservation in resectable disease or palliation in unresectable disease. DESIGN: All patients underwent evaluation by the multidisciplinary head and neck cancer team, with pathological diagnosis and staging. All patients underwent assessment for response to therapy using results of physical examination and radiologic imaging. Patients were followed up at 3-month intervals for a planned period of 5 years. SETTING: Academic center. PATIENTS: Thirty-eight previously untreated patients with newly diagnosed HNSCC were treated from June 1, 1996, through December 31, 1998, of whom 20 had resectable and 18 had unresectable tumors. INTERVENTION: Patients received intravenous cisplatin, 100 mg/m(2) for 1 hour on days 1 and 29; a 24-hour continuous infusion of fluorouracil, 1000 mg/m(2) on days 1 through 4 and 29 through 32; and radiation therapy, 150 rad twice daily for 12 days. The patients were given a 7- to 10-day break, and radiation therapy was restarted on day 29 for 12 additional days (total dose, 7200 rad). MAIN OUTCOME MEASURES: Complete, partial, and total response rates; disease-free survival; overall survival; and toxic effects. RESULTS: Toxic effects of treatment were moderately severe, including grades III to IV mucositis (89%), neutropenia (71%), and renal toxic effects (8%). In the 18 patients in the unresectable group, complete response in the 17 primary tumors and 15 cervical nodal metastases was achieved in 12 (71%) and 9 (60%), respectively; in the 20 patients undergoing organ preservation, complete response rates were 100% in the 23 primary tumors and 15 cervical nodal metastases. Complete response for all 38 patients was achieved in 31 (82%). In the unresectable group, the Kaplan-Meier relapse-free survival estimate is 56%, with follow-up from 29 to 45 months. In the organ preservation group, 75% of patients are alive without disease, and 8 have been followed up for 36 to 48 months. Of the 5 patients who have died, only 2 died of disease, with recurrences at 13.0 and 16.5 months. CONCLUSIONS: Chemoradiotherapy consisting of cisplatin, fluorouracil, and twice-daily external beam radiation is highly effective in achieving durable complete responses in patients with resectable HNSCC undergoing organ preservation and patients with unresectable HNSCC undergoing palliation. Toxic effects of this regimen were moderate to severe.

High tissue affinity angiotensin-converting enzyme inhibitors improve endothelial function and reduce infarct size.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors differ in their ability to inhibit tissue ACE. This study was, therefore, undertaken to determine whether high tissue affinity ACE inhibitors would improve endothelial function and thereby decrease tissue necrosis during ischemia. METHODS: In a porcine model, the second and third diagonal vessels were occluded for 90 minutes, followed by 45 minutes of cardioplegic arrest and 180 minutes of reperfusion. During the period of coronary occlusion, 10 pigs received enalaprilat (low affinity tissue ACE inhibitor), 0.05 mg/kg intravenously, 10 received quinaprilat (high affinity tissue ACE inhibitor), 10 mg intravenously, and 10 others received no ACE inhibitor. RESULTS: Wall motion scores (4, normal, to -1, dyskinesia) were higher in animals treated with ACE inhibitors (3.20+/-0.15 SE enalaprilat versus 3.08+/-0.23 quinaprilat versus 1.52+/-0.07 no ACE; both p < 0.0001 from no ACE). Endothelial-dependent relaxation to bradykinin was best preserved in the quinaprilat-treated hearts (32.1%+/-7.6% enalaprilat versus 65.8%+/-12.6% quinaprilat versus 30.6%+/-10.7% no ACE; p < 0.0001 from no ACE; p < 0.005 from enalaprilat). This was associated with a greater reduction in infarct size: area necrosis/area risk 24.3%+/-0.8% enalaprilat (p < 0.0001 from no ACE) versus 14.3%+/-3.2% quinaprilat (p < 0.0001 from no ACE; p < 0.005 from enalaprilat) versus 40.0%+/-1.7% no ACE. CONCLUSIONS: ACE inhibitors with higher affinity to tissue ACE result in better preservation of endothelial function and less tissue necrosis during coronary revascularization.

Drug interactions in palliative care.

PURPOSE: This review of drug interactions in palliative care examines the relevant literature in this area and summarizes the information on interactions of drugs, nutrients, and natural products that are used in the palliative care setting. Particular emphasis is placed on describing the newer information on the cytochrome P450 (CYP) system and the interactions of opioids, antidepressants, and the antitussive, dextromethorphan. METHODS: We performed a search of the MEDLINE database of the time period from 1966 until April 1998, using medical subject headings such as the names of selective serotonin reuptake inhibitors and other relevant medications in palliative care. Literature reviewed included both human and animal articles as well as non-English literature. Bibliographies of these articles and the personal libraries of several palliative care specialists were reviewed. Software developed by The Medical Letter-The Drug Interaction Program was also used. RESULTS: Drug interactions can be categorized in several ways. Drug-drug interactions are the most well known and can be kinetic, dynamic, or pharmaceutical. Pharmacokinetic interactions can involve CYP 2D6, which acts on drugs such as codeine and is responsible for its conversion to morphine. Poor metabolizers, either genotypic or due to phenocopying, are at risk for undertreatment if not recognized. Pharmacodynamic interactions with dextromethorphan may produce serotonin syndrome. CONCLUSION: Drug interactions are important in palliative care as in other aspects of medicine. These interactions are similar to those seen in other areas of medical care but have significant consequences in pain management. Failure to recognize these interactions can lead to either overdosing or undertreatment.

Primary tumors of the spine.

Primary osseous tumors of the spine are rare lesions and much less frequently encountered than metastases, multiple myeloma, and lymphoma. The interpreting radiologist must be aware of the typical radiographic appearance of the most common nonmyeloproliferative tumors of the spine because these tumors must be considered when a solitary spinal lesion is encountered. The purpose of this article is to describe the radiologic appearance and radiologic staging of the most common benign (hemangioma, enostosis, osteoid osteoma, osteoblastoma, giant cell tumor, aneurysmal bone cyst, and osteochondroma) and malignant (chordoma, chondrosarcoma, Ewing tumor, and osteosarcoma) osseous spine tumors.

Phase I trial of twice-weekly gemcitabine and concurrent radiation in patients with advanced pancreatic cancer.

PURPOSE: To determine the maximum-tolerated dose, dose-limiting toxicities, and potential antitumor activity of twice-weekly gemcitabine and concurrent radiation in patients with locally advanced pancreatic cancer. PATIENTS AND METHODS: Nineteen patients with histologically confirmed adenocarcinoma of the pancreas were studied at the Wake Forest University Baptist Medical Center and the University of North Carolina at Chapel Hill. The initial dose of gemcitabine was 20 mg/m(2) by 30-minute intravenous infusion each Monday and Thursday for 5 weeks concurrent with 50.4 Gy of radiation to the pancreas. Gemcitabine doses were escalated in 20-mg/m(2) increments in successive cohorts of three to six additional patients until dose-limiting toxicity was observed. RESULTS: The dose-limiting toxicities at 60 mg/m(2) given twice-weekly were nausea/vomiting, neutropenia, and thrombocytopenia. Twice-weekly gemcitabine at a 40-mg/m(2) dose was well tolerated. Of the eight patients eligible for a minimum follow-up of 12 months, three remain alive, one of whom has no evidence of disease progression. CONCLUSION: A dose of twice-weekly gemcitabine at 40 mg/m(2) produced mild thrombocytopenia, neutropenia, nausea, and vomiting when delivered with concurrent radiation to the upper abdomen in patients with advanced pancreatic cancer. These data suggest this regimen is well tolerated and may possess significant activity. These data and other observations have resulted in a phase II Cancer and Leukemia Group B study to ascertain the efficacy of this treatment regimen in patients with locally advanced pancreatic cancer.

Recognising clinical instability in hospital patients before cardiac arrest or unplanned admission to intensive care. A pilot study in a tertiary-care hospital.

OBJECTIVE: To investigate the nature and duration of clinical instability (i.e., abnormalities in simple physical observations or laboratory test results) in hospital patients before a "critical event" (i.e., a cardiac arrest or an unplanned admission to intensive care). DESIGN: Retrospective survey of medical records of all patients having critical events (CEs) over 12 months. Data on hospital and Intensive Care Unit (ICU) patients were obtained for comparison with the study population. SETTING: A 300-bed metropolitan teaching hospital with a seven-bed ICU. PATIENTS: All patients having CEs over a 12-month period (January to December 1997). MAIN OUTCOME MEASURES: Number of patients with clinical instability before a CE; duration of clinical instability before a CE; number of medical reviews of each patient before a CE; mortality rate and length of hospital stay for all patients. RESULTS: There were 122 CEs in 112 patients (median, 1; range, 1-4). Of the CEs, 79 were unplanned ICU admissions (14 subsequent to cardiac arrest calls), and 43 were cardiac arrest calls not resulting in ICU admission. Each CE was preceded by a median of two (range, 0-9) criteria for clinical instability. The median duration of instability before a CE was 6.5 hours (range, 0-432 hours), and in that time a median of two (range, 0-13) medical reviews took place. The incidence of CEs in the total hospital population (122 CEs/19,853 admissions) and in ICU patients (79 unplanned admissions/515 admissions) was 0.6% and 15%, respectively. There were 70 deaths (62%) among the 112 patients, compared with a total of 392 deaths (2% of admissions) in the hospital, of which 107 were in ICU. CONCLUSIONS: Very few patients suffer a CE while in hospital. However, those who do frequently manifest abnormalities in simple physical observations and laboratory test results before the CE. More rapid intervention in response to warning signs might provide a better outcome for these patients.

The evaluation of cocaine-induced chest pain with acute myocardial perfusion imaging.

OBJECTIVE: To use myocardial perfusion imaging to determine the etiology of cocaine-induced chest pain in patients without ECG evidence of acute cardiac ischemia. METHODS: The authors conducted a prospective study of consecutive consenting patients aged 18-70 years with cocaine-induced chest pain who reported cocaine use within three days and presented with a chief complaint of chest pain occurring within three hours and lasting longer than 15 minutes with a normal or nondiagnostic ECG. Patients were excluded if they had a clear-cut noncardiac cause of chest pain, ECG evidence of acute cardiac ischemia, history of myocardial infarction, pregnancy, or lactation, required immediate hospitalization, or were unable to consent. Patients were injected with Tc-99m tetrofosmin and imaged. Perfusion scans were independently read by two nuclear radiologists. Clinicians blinded to scan results determined patient disposition. Patients with abnormal scans were asked to return for follow-up resting scans. RESULTS: Fourteen patients were enrolled. Twelve of the 14 patients had chest pain at the time of Tc-99m tetrofosmin injection. Ten of the 14 [(71%) 95% CI = 48% to 95%] scans were normal or within normal limits. Four of the 14 [(29%) 95% CI = 5% to 52%] were abnormal. Of the four patients with abnormal scans, two had follow-up scans that demonstrated an irreversible perfusion abnormality, and two who did not return for follow-up reported no subsequent hospitalizations for acute cardiac ischemia. CONCLUSION: Perfusion imaging did not demonstrate reversible ischemia in most patients (12/14, 86%) with cocaine-induced chest pain without ECG evidence of ischemia. These results suggest that cocaine-induced chest pain in most patients without ECG evidence of ischemia is not due to acute ischemia.

Pilot study of local autologous tumor infiltrating lymphocytes for the treatment of recurrent malignant gliomas.

A prospective pilot study was performed in order to assess the safety of treating recurrent malignant gliomas (MGs) with locally infused autologous tumor infiltrating lymphocytes (TILs) and recombinant interleukin-2 (rIL-2). Six patients were entered between June 27, 1994 and June 2, 1995 and followed until July 1, 1998. At surgery an Ommaya reservoir was placed for later infusion of TILs and rIL-2. Following surgery, autologous TILs were expanded in vitro in the presence of rIL-2 and infused on treatment days 1 and 14, with concurrent rIL-2 infusions performed three times each week for one month. Following completion of immunotherapy all patients were offered chemotherapy. Phenotypic analysis demonstrated TILs to be T-lymphocytes (87-99% CD3+). Of these, 4 of 6 cases (67%) phenotyped as cytotoxic/suppressor T-lymphocytes (CD8+) and 2 of 6 cases (33%) phenotyped as helper/inducer T-lymphocytes (CD4+). TILs demonstrated limited selective cytotoxicity, with dose dependent cytotoxicity against autologous tumor, allogenic tumor and long term MG cell lines. There were no significant (Grade 3 or 4) complications. One patient developed transient low grade fevers, and 2 developed asymptomatic hydrocephalus. All patients developed transient and asymptomatic cerebral swelling, noted on the immediate post-treatment imaging studies. At three and six month follow-up, 3 patients responded with partial response, 2 demonstrated stable disease and 1 patient progressed. At long term follow-up, 1 patient had a complete response (45 month follow-up), 2 had a partial response (48 and 47 month follow-up) and 3 patients expired as a result of progressive disease (at 12, 12 and 18 months following immunotherapy). A relationship between subsequent chemotherapy or extent of resection to outcome was not apparent but could not be excluded. This pilot study demonstrated that locally infused autologous TILs and rIL-2 could be delivered without serious toxicity. Further studies are indicated to determine the safety and long term efficacy of TIL immunotherapy.

Use of the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI) to assist with triage of patients with chest pain or other symptoms suggestive of acute cardiac ischemia. A multicenter, controlled clinical trial.

BACKGROUND: Approximately 6 million U.S. patients present to emergency departments annually with symptoms suggesting acute cardiac ischemia. Triage decisions for these patients are important but remain difficult. OBJECTIVE: To test whether computerized prediction of the probability of acute ischemia, used with electrocardiography, improves the accuracy of triage decisions. DESIGN: Controlled clinical trial. SETTING: 10 hospital emergency departments in the midwestern, southeastern, and northeastern United States. PATIENTS: 10689 patients with chest pain or other symptoms suggestive of acute cardiac ischemia. INTERVENTION: The probability of acute ischemia predicted by the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI), either automatically printed or not printed on patients' electrocardiograms. MEASUREMENTS: Emergency department triage to a coronary care unit (CCU), telemetry unit, ward, or home. Other measurements were the bed capacity of the CCU relative to that of the telemetry unit; training or supervision status of the triaging physician; and patient diagnoses and outcomes based on clinical, electrocardiographic, and creatine kinase data. RESULTS: For patients without cardiac ischemia, in hospitals with high-capacity CCUs and relatively low-capacity cardiac telemetry units, use of ACI-TIPI was associated with a reduction in CCU admissions from 15% to 12%, a change of -16% (95% CI, -30% to 0%), and an increase in emergency department discharges to home from 49% to 52%, a change of 6% (CI, 0% to 14%; overall P=0.09). Across all hospitals, for patients evaluated by unsupervised residents, use of ACI-TIPI was associated with a reduction in CCU admissions from 14% to 10%, a change of -32% (CI, -55% to 3%); a reduction in telemetry unit admissions from 39% to 31%, a change of -20% (CI, -34% to -2%); and an increase in discharges to home from 45% to 56%, a change of 25% (CI, 8% to 45%; overall P=0.008). Among patients with stable angina, in hospitals with high-capacity CCUs, use of ACI-TIPI was associated with a reduction in CCU admissions from 26% to 13%, a change of -50% (CI, -70% to -17%), and an increase in discharges to home from 20% to 22%, a change of 10% (CI, -29% to 71%; overall P=0.02). At hospitals with high-capacity telemetry units, use of ACI-TIPI was associated with a reduction in telemetry unit admissions from 68% to 59%, a change of -14% (CI, -27% to 1%), and an increase in emergency department discharges to home from 10% to 21%, a change of 100% (CI, 22% to 230%; overall P=0.02). Among patients with acute myocardial infarction or unstable angina, use of ACI-TIPI did not change appropriate admission (96%) to the CCU or telemetry unit at hospitals with high-capacity CCUs or telemetry units. CONCLUSIONS: Use of ACI-TIPI was associated with reduced hospitalization among emergency department patients without acute cardiac ischemia. This result varied as expected according to the CCU and cardiac telemetry unit capacities and physician supervision at individual hospitals. Appropriate admission for unstable angina or acute infarction was not affected. If ACI-TIPI is used widely in the United States, its potential incremental impact may be more than 200000 fewer unnecessary hospitalizations and more than 100000 fewer unnecessary CCU admissions.