Implication of Major Adverse Postoperative Events and Myocardial Injury on Disability and Survival: A Planned Subanalysis of the ENIGMA-II Trial.

BACKGROUND: Globally, >300 million patients have surgery annually, and ≤20% experience adverse postoperative events. We studied the impact of both cardiac and noncardiac adverse events on 1-year disability-free survival after noncardiac surgery. METHODS: We used the study cohort from the Evaluation of Nitrous oxide in Gas Mixture of Anesthesia (ENIGMA-II) trial, an international randomized trial of 6992 noncardiac surgical patients. All were ≥45 years of age and had moderate to high cardiac risk. The primary outcome was mortality within 1 postoperative year. We defined 4 separate types of postoperative adverse events. Major adverse cardiac events (MACEs) included myocardial infarction (MI), cardiac arrest, and myocardial revascularization with or without troponin elevation. MI was defined using the third Universal Definition and was blindly adjudicated. A second cohort consisted of patients with isolated troponin increases who did not meet the definition for MI. We also considered a cohort of patients who experienced major adverse postoperative events (MAPEs), including unplanned admission to intensive care, prolonged mechanical ventilation, wound infection, pulmonary embolism, and stroke. From this cohort, we identified a group without troponin elevation and another with troponin elevation that was not judged to be an MI. Multivariable Cox proportional hazard models for death at 1 year and assessments of proportionality of hazard functions were performed and expressed as an adjusted hazard ratio (aHR) and 95% confidence intervals (CIs). RESULTS: MACEs were observed in 469 patients, and another 754 patients had isolated troponin increases. MAPEs were observed in 631 patients. Compared with control patients, patients with a MACE were at increased risk of mortality (aHR, 3.36 [95% CI, 2.55-4.46]), similar to patients who suffered a MAPE without troponin elevation (n = 501) (aHR, 2.98 [95% CI, 2.26-3.92]). Patients who suffered a MAPE with troponin elevation but without MI had the highest risk of death (n = 116) (aHR, 4.29 [95% CI, 2.89-6.36]). These 4 types of adverse events similarly affected 1-year disability-free survival. CONCLUSIONS: MACEs and MAPEs occur at similar frequencies and affect survival to a similar degree. All 3 types of postoperative troponin elevation in this analysis were associated, to varying degrees, with increased risk of death and disability.

Changes in mouse granulosa cell gene expression during early luteinization.

Changes in gene expression during granulosa cell luteinization have been measured using serial analysis of gene expression (SAGE). Immature normal mice were treated with pregnant mare serum gonadotropin (PMSG) or PMSG followed, 48 h later, by human chorionic gonadotropin (hCG). Granulosa cells were collected from preovulatory follicles after PMSG injection or PMSG/hCG injection and SAGE libraries generated from the isolated mRNA. The combined libraries contained 105,224 tags representing 40,248 unique transcripts. Overall, 715 transcripts showed a significant difference in abundance between the two libraries of which 216 were significantly down-regulated by hCG and 499 were significantly up-regulated. Among transcripts differentially regulated, there were clear and expected changes in genes involved in steroidogenesis as well as clusters of genes involved in modeling of the extracellular matrix, regulation of the cytoskeleton and intra and intercellular signaling. The SAGE libraries described here provide a base for functional investigation of the regulation of granulosa cell luteinization.

A canine model of gastroesophageal reflux disease (GERD).

BACKGROUND: Although a variety of antireflux procedures and medications are used to treat gastroesophageal reflux disease (GERD), reliable large-animal models of GERD that can be used to objectively compare the efficacy of these treatments are lacking. METHODS: Esophageal manometry and 24-h gastroesophageal pH monitoring with event data were performed in 18 mongrel dogs with a cervical esophagopexy. We then calculated a modified DeMeester score: The Duke Canine reflux score (DCR). Thereafter, the animals underwent a 4-cm anterior distal esophageal myotomy, incision of the left diaphragmatic crus, and intrathoracic gastric cardiopexy. Postoperative 24-h pH and manometry were obtained 2 weeks later. RESULTS: The postoperative 24-h pH results showed a significant increase in the mean DCR score (5.9 +/- 4.5 vs 84.9 +/- 56.1, p < 0.0002), and manometry indicated a significant decrease in mean lower esophageal sphincter (LES) pressure (7.1 +/- 2.9 vs 3.2 +/- 2.5 mmHg, p < 0.0001). CONCLUSION: This technique reliably creates a canine model of GERD.

Surgical resection is necessary to maximize tumor control in function-preserving, aggressive chemoradiation protocols for advanced squamous cancer of the head and neck (stage III and IV).

BACKGROUND: The role of surgery in aggressive chemoradiation protocols for advanced head and neck cancer has been questioned because of the quoted high clinical response rates in many series. METHODS: The role of surgical resection was examined in an aggressive neoadjuvant protocol of weekly paclitaxel, carboplatin, and radiation for stage III and IV with completion of radiation to 72 Gy if biopsy at the primary site was negative after administration of 45 Gy. Of 43 patients enrolled, 38 completed the protocol. The clinical response was 100% (including 18 complete and 20 partial responses). RESULTS: The complete pathologic response (negative primary site biopsy at 45 Gy) was 25 of 38 (66%). Of patients who presented with N1 to N3 nodes, neck dissection revealed residual nodal metastases in 22%. Surgical resection of the primary site was required in 13 patients, including 5 with larynx cancer and 2 with base of tongue cancers. Four patients had resection with reconstruction for advanced mandible floor of mouth cancer, and one had resection of nasal-maxillary cancer. Functional resection was performed in 9 of 12 patients. The median progression free and overall survival was 64% and 68%, respectively, at median follow-up of 50 months. Nine patients developed recurrence (three local and six distant). There were no failures in the neck. Salvage surgery was performed in one patient with local and one with distant disease. CONCLUSIONS: Surgical resection is an essential component of aggressive chemoradiation protocols to ensure tumor control at the primary site and in the neck.

Simple predictors of uvulopalatopharyngoplasty outcome in the treatment of obstructive sleep apnea.

STUDY OBJECTIVE: Our objective was to determine whether baseline polysomnography, cephalometry, and anthropometry data could predict uvulopalatopharyngoplasty (UPPP) success or failure. DESIGN: We retrospectively reviewed polysomnography, cephalometry, and anthropometry data from patients who underwent UPPP for obstructive sleep apnea (OSA). SETTING: A university medical center. PATIENTS: OSA was diagnosed by polysomnography in 46 patients who underwent UPPP surgery for their sleep disorder. INTERVENTIONS: UPPP surgery with/or without tonsillectomy. MEASUREMENTS AND RESULTS: The mean patient age was 43 years, and the mean body mass index was 32.5 kg/m(2). The mean presurgical apnea-hypopnea index (AHI) was 45, and the mean baseline nadir oxygen saturation was 81%. Successful surgery was defined as a reduction in AHI to < 10 or to < 20 with a 50% reduction from the patient's baseline AHI. Of the 46 patients, 16 were successfully treated and 30 did not respond to surgical treatment. A mandibular-hyoid distance (MP-H) > 20 mm was found to be significantly (p = 0.05) predictive of failure of UPPP. When stepwise regression analysis was performed utilizing postsurgical AHI as the dependent variable and presurgical AHI, age, body mass index, baseline nadir O(2) saturation, and five cephalometric measurements as independent variables, MP-H distance significantly (r = 0.524; p = 0.01) correlated positively with postsurgical AHI. The distance between the superior point of a line-constructed plane of the sphenoidale (parallel to Frankfort horizontal) and a point at the intersection of the palatal plane perpendicular to the hyoid correlated negatively with postsurgical AHI (r = 0.586; p = 0.05). By creating a logistic model of this data, an MP-H distance < 21 mm, an angle created by point A to the nasion to point B < 3 degrees, and the presence of a baseline AHI < 38 enhanced the predictability of UPPP success. CONCLUSIONS: The presence of a baseline AHI < 38 and an MP-H < or = 20 mm, and the absence of retrognathia are predictors of improvement after UPPP. Based on these findings, we would advocate the continued evaluation of cephalometric measurements and careful consideration of surgical treatment options for OSA.

The stability of lactate concentration in preserved blood microsamples.

This study aimed to determine the stability of lactate concentration in blood samples preserved and stored using methods practical for field testing and experimental applications. Whole blood microsamples were obtained from venous samples drawn from 10 healthy subjects following bouts of moderate (approximately 5 mmol x l(-1), n = 12), or intense (approximately 10 mmol x l(-1), n = 12), treadmill exercise. Samples were analysed fresh (2 x 25 microl), or placed in preservative-containing tubes (12 x 75 microl) and analysed directly, or after storage at room temperature (RT) or 4 degrees C, for 1 h, 18 h, 2 d, 3 d or 7 d, or at -20 degrees C for 7 d. In comparison to preserved samples assayed directly after collection, lactate levels in all RT samples had declined significantly, whereas the 4 degrees C samples had not changed, by 2 d post-collection. After 7 d of refrigeration, the absolute value of the difference from lactate levels in samples measured after collection (mean +/- SD) was 0.38 +/- 0.34 mmol x l(-1), or 5.3 +/- 4.3%; with freezing, this difference was 0.27 +/- 0.27 mmol x l(-1), or 3.6 +/- 3.0%. These differences were less than the daily variation in the analyser readings of a 10 mmol x l(-1) standard, indicating that the blood preservation and storage methods identified herein are suitable for use during exercise testing.

Anaesthesia and postoperative pain management for bilateral lung volume reduction surgery.

Bilateral lung volume reduction surgery was introduced into Australia in 1995 for treatment of selected patients with emphysema. We present our experience of the anaesthetic management of our first 55 cases and describe factors associated with outcome. There were four postoperative deaths (7%). Mean (SD) total operation time was 231 (72) minutes. Median intensive care unit (ICU) stay was 26 hours. There was a significant improvement in postoperative lung function (FEV1, VC, 6-minute walk test, all P < 0.001). Eight patients (15%) required reintubation for respiratory failure; three of these patients subsequently died. With multivariate analysis, total operation time was the only significant predictor of length of ICU stay R2 = 0.25, P = 0.001), which itself was the only significant predictor of hospital stay duration (R2 = 0.36, P < 0.001).

Randomized trial of informed consent and recruitment for clinical trials in the immediate preoperative period.

BACKGROUND: The standard process of obtaining informed consent sometimes prevents physicians or patients from participating in clinical trials, partly because they are concerned about eventual treatment allocation or the physician is concerned the patient might harbor some uncertainty about the best treatment. Alternative randomization methods have been advocated that may address these and other concerns. METHODS: After institutional ethics committee gave its approval, the authors interviewed 770 patients before operation and asked them to consider enrolling in a mock anesthesia trial. Patients were allocated randomly to one of five methods of randomization and consent: one-sided informed consent (the most common approach), prerandomized consent to experimental treatment, prerandomized consent to standard treatment, one-sided physician-modified informed consent, or one-sided patient-modified informed consent. Recruitment rates were compared and sociodemographic and perioperative predictors of recruitment were identified. RESULTS: The randomization method did not result in any significant difference in recruitment rates: one-sided informed consent, 55.6%; prerandomized consent to experimental treatment, 53.3%; prerandomized consent to standard treatment, 53%; one-sided physician-modified informed consent, 60.7%; and one-sided patient-modified informed consent, 56.7% (P = 0.66). Multivariate predictors of recruitment were patient age >45 yr (odds ratio, 1.44; 95% confidence interval [CI], 1.08 to 1.93), English-speaking at home (1.49; 1.0 to 2.21), and male researcher-male patient interaction (1.37; 1.20 to 1.57). CONCLUSIONS: No evidence emerged that alternative randomization and consent designs resulted in increased recruitment rates compared with simple one-sided informed consent for a sham anesthesia trial in patients awaiting elective surgery. Older, male patients were more likely to provide consent.

Bilateral synchronous tonsillar carcinoma.

Synchronous cancers occur in four per cent of patients with head and neck malignancies but no bilateral synchronous tonsillar carcinomas have been described in the English literature. We describe the first such case and discuss the prognostic aspect of this carcinoma. In the presence of contralateral neck nodes in patients with head and neck malignancies, a careful search should be made for a second head and neck primary.

Chemoradiotherapy for advanced inoperable head and neck cancer: A phase II study.

The beneficial effects of chemotherapy in patients with advanced head and neck cancer remain controversial in terms of survival, but have shown some promise in improving locoregional control and quality of life. In an effort to improve locoregional control and survival, a prospective phase II study was initiated using paclitaxel and carboplatin with concurrent conventional fractionated external-beam radiotherapy. Paclitaxel and carboplatin have both shown excellent radiosensitization through two discrete mechanisms, cell blockage in G2/M phase and inhibition of DNA repair, respectively. Patients were stratified as either operable or inoperable. This report pertains to the inoperable patient group, who received eight cycles of weekly paclitaxel (60 mg/m2), carboplatin (area under the concentration-time curve of 1) with conventional radiotherapy (72 Gy). Chemoradiotherapy was followed by neck dissection for those patients who presented with clinically palpable lymph nodes. Thirty-three patients were enrolled in this group (23 men and 10 women with a median age of 56 years). Eleven patients (33%) had stage III disease; 22 (67%), stage IV disease. The median follow-up period was 14 months. Clinical complete response occurred in 20 patients (60%) and partial response occurred in 10 (30%), for an overall response rate of 90%. Following completion of therapy, 18 patients have undergone biopsy at the primary tumor site and 17 were negative. Eight of the 16 patients with clinically palpable neck nodes at presentation underwent neck dissection; five (63%) had negative nodes. Mucositis was the most common toxicity. Grade 3 or 4 mucositis occurred in 30 of the 33 (90%) patients. Other grade 3 or 4 toxicities included skin (22%), candidiasis (19%), neutropenia (9%), and dehydration (6%). One patient with laryngeal carcinoma who had pathologic complete response developed cartilage necrosis and is undergoing hyperbaric oxygen therapy. Survival data are early but encouraging. Concurrent paclitaxel, carboplatin, and external-beam radiotherapy yielded excellent clinical and pathologic responses. Mucositis remains the most common and significant morbidity. The study will continue for necessary accrual.

Preoperative paclitaxel, carboplatin, and radiation therapy in advanced head and neck cancer (stage III and IV).

Preoperative chemotherapy and chemoradiation protocols are generally associated with high clinical response rates but limited pathologic responses for large primary tumors. We have initiated a prospective phase II study of weekly paclitaxel and carboplatin plus concurrent, fractionated external-beam radiation, followed by organ-preserving or function-restorative surgery (when applicable to maximize locoregional tumor control). Operable patients staged by triple endoscopy received a percutaneous gastrostomy and vigorous dental and nutritional support during therapy. Paclitaxel 60 mg/m2 and carboplatin at an area under the concentration-time curve of 1 were administered weekly with radiation therapy 45 Gy, with repeat biopsy of the primary site at 5 weeks. Patients with a positive biopsy had definitive surgery within 4 to 5 weeks. Patients with a negative biopsy received 3 additional weeks of radiation therapy, to a total dose of 72 Gy plus paclitaxel and carboplatin. Forty-three patients were enrolled, including 33 men and 10 women ranging in age from 37 to 81 years. Fourteen patients had stage III disease, 19 patients had stage IVA disease, and 10 patients had stage IVB disease. Sites of disease included the floor of the mouth (n = 8), tongue (n = 8), oropharynx (n = 5), hypopharynx (n = 4), larynx (n = 12), palate-tonsil (n = 2), unknown primary (n = 3), and nasal cavity (n = 1). Of 38 patients evaluable for primary response (two patients had unknown primary tumor, two patients failed to complete the chemoradiation protocol, and one patient was evaluable for toxicity only), 18 patients had a complete clinical response and 20 patients had a partial response; the overall clinical response rate was 100%. A pathologic clinical response at the primary site occurred in 25 of these 38 patients (66%), who subsequently received completion radiation (67 to 72 Gy). After induction chemoradiation, 36 patients with N1-N3 nodes had neck dissection; seven had positive nodes (19%). Fourteen patients had residual cancer at the primary site at the time of the repeat biopsy. Sites of the lesions were the floor of the mouth/mandible (n = 4), nasal cavity/maxilla (n = 2), base of tongue (n = 2), and larynx (n = 6). All were resected with function-preserving reconstruction (two patients required total laryngectomy and one patient refused surgery). At a median follow-up of more than 16 months, progression-free and overall survival rates were 64% and 68%, respectively. Preoperative paclitaxel, carboplatin, and radiation was associated with a high clinical response rate at the primary site and a high level of organ preservation or functional restoration, if ablation was performed.

Clonidine and cardiac surgery: haemodynamic and metabolic effects, myocardial ischaemia and recovery.

Clonidine may have beneficial effects in patients undergoing major surgery. We enrolled 156 patients having elective CABG surgery in a double-blind, randomized trial. Patients were randomized to receive either two doses of placebo (Group PP) or clonidine 5 micrograms/kg (Group CC). Perioperative measurements included haemodynamics, anaesthetic and analgesic drug usage, creatinine clearance, cortisol excretion, recovery times and quality of life (SF-36) after surgery. Overall, there was no significant difference with time to tracheal extubation (median [10-90 centile]): CC 7.1 (3.4-18) h vs PP 8.0 (4.3-17) h, P = 0.70; but there was a higher proportion of patients extubated within four hours: CC 20% vs. PP 8%, P = 0.038. Clonidine resulted in a number of significant (P < 0.05) haemodynamic changes, particularly pre-CPB: less tachycardia and hypertension, more bradycardia and hypotension. Clonidine was associated with a significant (P < 0.05) reduction in anaesthetic drug usage, higher creatinine clearance, lower cortisol excretion and improvement in some aspects of quality of life. This study lends support to consideration of clonidine therapy in patients undergoing CABG surgery.

The effect of forced air warming on postoperative oxygen consumption and temperature in elective orthopaedic surgery.

Actively warming patients during surgery is considered the best method of preventing inadvertent hypothermia. In order to investigate the effect of forced air warming on postoperative oxygen consumption, we studied 26 patients undergoing orthopaedic surgery using a prospective, randomized trial design. We measured oxygen consumption, carbon dioxide production, temperature, thermal comfort and pain scores. Apart from intraoperative temperature, there were no significant differences in these measurements between the two groups. This study demonstrated the gradual heat gain and also the potential for hyperthermia from pre- and intraoperative forced air warming. We conclude that forced air warming is not necessary for moderate duration non-body-cavity surgery if effective preinduction covering of patients and minimal surgical exposure is achieved.

Preoperative chemoradiation coupled with aggressive resection as needed ensures near total control in advanced head and neck cancer.

BACKGROUND: Preoperative chemotherapy or chemoradiation protocols are generally associated with high clinical response rates, but limited pathologic responses for large primary tumors. We have initiated a prospective phase II study of weekly paclitaxel 60 mg/M2, and carboplatin (AUC of 1) plus concurrent fractionated external beam radiation (45 Gy) followed by organ-preserving (or function restorative) surgery when applicable to maximize local-regional tumor control. PATIENTS AND METHODS: Operable patients staged by triple endoscopy received a percutaneous endoscopic gastrostomy and vigorous dental and nutritional support during therapy. Weekly paclitaxel 60 mg/M2, carboplatin (AUC of 1), and radiation 45 Gy were given with rebiopsy of the primary site at 5 weeks. Patients with positive biopsy had definitive surgery in 4 to 5 weeks. Patients with negative biopsy-results received 3 additional weeks of radiation, to a total dose of 72 Gy plus carboplatin and paclitaxel. RESULTS: The 35 patients were 29 men and 6 women, aged 40 to 71 years, with stage III (12) or stage IV (23) cancer. The site of the cancer was oral cavity, 10; base of tongue, 3; oropharynx, 3; hypopharynx, 4; larynx, 12 (glottic, 6; supraglottic, 6), unknown primary, 2; other, nasal cavity, 1. Of 34 evaluable patients, 16 (47%) had a complete clinical response (CR) and 18 (53%) had a partial response (PR); total clinical response rate was 100%. A pathologic CR at the primary site occurred in 23 of 34 patients (68%; 2 had an unknown primary) who went on to completion radiation at 67 to 72 Gy. After induction chemoradiation 21 patients with N1-3 nodes had neck dissection; 6 (31%) had positive nodes. Twelve patients had residual cancer at the primary site at time of rebiopsy: mandible, 4; maxilla, 1; base of tongue, 2; larynx, 4; floor of mouth, 1; and nasal cavity, 1. All were resected with function-preserving reconstruction. At median follow-up of >12 months, progression-free and overall survivals were 71% and 83%, respectively. CONCLUSION: Preoperative treatment with paclitaxel, carboplatin, and radiation is associated with high CR at the primary site and a high level of organ preservation or functional restoration if ablation is done.

Hemodynamic effects, myocardial ischemia, and timing of tracheal extubation with propofol-based anesthesia for cardiac surgery.

Recent interest in earlier tracheal extubation after coronary artery bypass graft (CABG) surgery has focused attention on the potential benefits of a propofol-based technique. We randomized 124 patients (34 with poor ventricular function) undergoing CABG surgery to receive either a propofol-based (5 mg.kg-1.h-1 prior to sternotomy, 3 mg.kg-1. h-1 thereafter; n = 58) or enflurane-based (0.2%-1.0%, n = 66) anesthetic. Induction of anesthesia consisted of fentanyl 15 micrograms/kg and midazolam 0.05 mg/kg intravenously in both groups. The enflurane group received an additional bolus of fentanyl 5 micrograms/kg prior to sternotomy and fentanyl 10 micrograms/kg with midazolam 0.1 mg/kg at commencement of cardiopulmonary bypass (CPB). Patients receiving propofol were extubated earlier (median 9.1 h versus 12.3 h, P = 0.006), although there was no difference in time to intensive care unit (ICU) discharge (both 22 h, P = 0.54). Both groups had similar hemodynamic changes throughout (all P > 0.10), as well as metaraminol (P = 0.49) and inotrope requirements (P > 0.10), intraoperative myocardial ischemia (P = 0.12) and perioperative myocardial infarction (P = 0.50). The results of this trial suggest that a propofol-based anesthetic, when compared to an enflurane-based anesthetic requiring additional dosing of fentanyl and midazolam for CPB, can lead to a significant reduction in time to extubation after CABG surgery, without adverse hemodynamic effects, increased risk of myocardial ischemia or infarction.

The magnitude of random errors in acoustic rhinometry and re-interpretation of the acoustic profile.

By measuring the effect of incomplete acoustic seal and increasing nosepiece insertion depth on the derived nasal acoustic profile, this study quantifies the random errors that may arise in the course of the clinical practice of acoustic rhinometry using the insert nosepiece. The relative movement of the nose and nosepiece also enables us to separate the contribution of each to the acoustic curve. Sixteen volunteers were tested using a commercial rhinometer. As a consequence of this study we are able to formulate the following conclusions: (1) The first minimum of the nasal acoustic profile is due to the end of the nosepiece, but may be further diminished by the position of the nosepiece tip on or within the nose. (2) The second minimum is due to the nasal valve, to which the head of the inferior turbinate contributes. (3) Acoustic rhinometry is extremely sensitive to acoustic leaks and results obtained without a fluid acoustic sealant cannot be considered valid. (4) The errors associated with the nosepiece insertion technique are very small unless the nosepiece is forced into the nasal vestibule.

Concurrent paclitaxel, carboplatin, and radiotherapy in advanced head and neck cancers: a phase II study--preliminary results.

Radiotherapy or surgery alone for advanced head and neck cancer generally yields poor results. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin have both shown excellent radiosensitization through two discrete mechanisms, namely, blocking the cell cycle in the G2/M phase and inhibiting DNA repair. In an effort to improve locoregional control and survival, a prospective phase II study was initiated using paclitaxel 60 mg/ml and carboplatin (area under the concentration-time curve of 1), each given as a single dose weekly with concurrent conventional fractionated external beam radiotherapy. Patients were stratified into two groups: operable and inoperable/unresectable. The operable and inoperable groups received 5 weeks (45 Gy) and 8 weeks (72 Gy) of chemoradiotherapy, respectively. Patients in the operable group were evaluated with repeat biopsies from the primary site after 5 weeks. Those with a positive biopsy underwent surgery; those with a negative biopsy received 3 additional weeks of chemoradiotherapy. Thirty-four patients were entered in the operable group (28 men and six women; 40 to 71 years of age; 12 stage III and 22 stage IV). Of 26 evaluable patients, 19 (73%) had a complete clinical response (95% confidence interval [CI], 52% to 88%) and six (23%) had a partial response (95% CI, 9% to 44%), for a total clinical response rate of 96% (95% CI, 80% to 100%). A pathologic complete response at the primary site (two had an unknown primary site) occurred in 17 of 24 (71%) patients (95% CI, 49% to 87%). Of 20 patients with N1-3 nodes who underwent neck dissection, 17 (85%) had pathologically negative lymph nodes. Seven patients with residual tumor at the primary site were resected (oral cavity, three; maxilla, one; base of tongue, one; and larynx, two). Grades 3 and 4 mucositis were seen in 19 (73%) patients; mucositis was the most common and significant morbidity. Accrual for the inoperable group continues. Concomitant paclitaxel, carboplatin, and external beam radiotherapy yielded excellent clinical responses, but produced significant grade 3/4 toxicity. In the operable group, the majority of responders had a complete pathologic response. These preliminary findings will be assessed in terms of response duration, organ preservation, and long-term survival.

Unusual complication of nasal CPAP: subcutaneous emphysema following facial trauma.

Subcutaneous emphysema is an unusual complication of nasal continuous positive airway pressure (CPAP). We report a case of a 58-year-old man who fell and sustained mild facial trauma to the left side of his head. After using CPAP the following night, he developed diffuse subcutaneous emphysema of his face and left neck. He discontinued CPAP, and his symptoms improved. The potential mechanisms of this patient's subcutaneous emphysema and the prior reports of this complication following facial trauma or dental procedure without use of CPAP are reviewed. Although there are case reports of bacterial meningitis and pneumocephalus following use of nasal CPAP, we are not aware of any prior reports of subcutaneous emphysema following use of CPAP. In light of our experience and the above related case reports, we would suggest nasal CPAP be withheld temporarily in the setting of acute facial trauma.

Association between oxygen delivery and consumption in patients undergoing cardiac surgery. Is there supply dependence?

We studied the relationship between oxygen delivery (DO2) and consumption (VO2) in twenty patients undergoing cardiac surgery, in order to determine if VO2 was dependent on DO2 (pathological oxygen supply dependence). We measured VO2 from expired gas analysis (VO2G) and compared this to that calculated using the reverse Fick method (VO2F). Both VO2G and VO2F increased after cardiopulmonary bypass (P < 0.001), without change in DO2 (i.e. oxygen extraction ration increased). There was a significant relationship between changes in DO2 and VO2F, both before bypass (r = 0.74, P < 0.001) and after bypass (r = 0.69, P < 0.001), while changes in DO2 and VO2G had no such relationship (pre-bypass: r = 0.38, P = 0.094; post-bypass: r = 0.10, P = 0.68). There was poor agreement between VO2F and VO2G perioperatively. We could not demonstrate supply dependence in elective cardiac surgical patients.