The who, where, and what of rapid sequence intubation: prospective observational study of emergency RSI outside the operating theatre.

BACKGROUND: Emergency rapid sequence intubation (RSI) performed outside the operating room on emergency patients is the cornerstone of emergency airway management. Complication rates are unknown for this procedure in the United Kingdom and the factors contributing to immediate complications have not been identified. AIMS: To quantify the immediate complications of RSI and to assess the contribution made by environmental, patient, and physician factors to overall complication rates. METHODS: Prospective observational study of 208 consecutive adult and paediatric patients undergoing RSI over a six month period. RESULTS: Patients were successfully intubated by RSI in all cases. There were no deaths during the procedure and no patient required a surgical airway. Patient diagnostic groups requiring RSI are described. Immediate complications were hypoxaemia 19.2%, hypotension 17.8%, and arrhythmia 3.4%. Hypoxaemia was more common in patients with pre-existing respiratory or cardiovascular conditions than in patients with other diagnoses (p<0.01). Emergency department intubations were associated with a significantly lower complication rate than other locations (16.9%; p = 0.004). This can be explained by the difference in diagnostic case mix. Intubating teams comprised anaesthetists, non-anaesthetists, or both. There were no significant differences in complication rates between these groups. CONCLUSIONS: RSI has a significant immediate complication rate, although the clinical significance of transient events is unknown. The likelihood of immediate complications depends on the patient's underlying condition, and relevant diagnoses should be emphasised in airway management training. Complication rates are comparable between anaesthetists and non-anaesthetists. The significantly lower complication rates in emergency department RSI can be explained by a larger proportion of patients with comparatively stable cardiorespiratory function.

Teaching old dogs new tricks--a personal perspective on a decade of efforts by a clinical ethics committee to promote awareness of medical ethics.

To incorporate medical ethics into clinical practice, it must first be understood and valued by health care professionals. The recognition of this principle led to an expanding and continuing educational effort by the ethics committee of the Vancouver General Hospital. This paper reviews this venture, including some pitfalls and failures, as well as successes. Although we began with consultants, it quickly became apparent that education in medical ethics must reach all health care professionals--and medical students as well. Our greatest successes came in the formative years of a medical career (i.e., in medical school and residency training programmes), but other efforts were not wasted, particularly among nurses and other health care professionals. Although this is a personal review of the experience in one institution, the lessons learnt in Vancouver are applicable to the further development of medical ethics in the UK.

Propofol vs midazolam for ICU sedation : a Canadian multicenter randomized trial.

STUDY OBJECTIVES: To determine whether sedation with propofol would lead to shorter times to tracheal extubation and ICU length of stay than sedation with midazolam. DESIGN: Multicenter, randomized, open label. SETTING: Four academic tertiary-care ICUs in Canada. PATIENTS: Critically ill patients requiring continuous sedation while receiving mechanical ventilation. INTERVENTIONS: Random allocation by predicted requirement for mechanical ventilation (short sedation stratum, < 24 h; medium sedation stratum, > or = 24 and < 72 h; and long sedation stratum, > or = 72 h) to sedation regimens utilizing propofol or midazolam. MEASUREMENTS AND RESULTS: Using an intention-to-treat analysis, patients randomized to receive propofol in the short sedation stratum (propofol, 21 patients; midazolam, 26 patients) and the long sedation stratum (propofol, 4 patients; midazolam, 10 patients) were extubated earlier (short sedation stratum: propofol, 5.6 h; midazolam, 11.9 h; long sedation stratum: propofol, 8.4 h; midazolam, 46.8 h; p < 0.05). Pooled results showed that patients treated with propofol (n = 46) were extubated earlier than those treated with midazolam (n = 53) (6.7 vs 24.7 h, respectively; p < 0.05) following discontinuation of the sedation but were not discharged from ICU earlier (94.0 vs 63.7 h, respectively; p = 0.26). Propofol-treated patients spent a larger percentage of time at the target Ramsay sedation level than midazolam-treated patients (60.2% vs 44.0%, respectively; p < 0.05). Using a treatment-received analysis, propofol sedation either did not differ from midazolam sedation in time to tracheal extubation or ICU discharge (sedation duration, < 24 h) or was associated with earlier tracheal extubation but longer time to ICU discharge (sedation duration, > or = 24 h, < 72 h, or > or = 72 h). CONCLUSIONS: The use of propofol sedation allowed for more rapid tracheal extubation than when midazolam sedation was employed. This did not result in earlier ICU discharge.

Is a low transfusion threshold safe in critically ill patients with cardiovascular diseases?

OBJECTIVE: To compare a restrictive red blood cell transfusion strategy with a more liberal strategy in volume-resuscitated critically ill patients with cardiovascular disease. SETTING: Twenty-two academic and three community critical care units across Canada. STUDY DESIGN: Randomized controlled clinical trial. STUDY POPULATION: Three hundred fifty-seven critically ill patients with cardiovascular diseases from the Transfusion Requirements in Critical Care trial who had a hemoglobin concentration of <90 g/L within 72 hrs of admission to the intensive care unit. INTERVENTIONS: Patients were randomized to a restrictive strategy to receive allogeneic red blood cell transfusions at a hemoglobin concentration of 70 g/L (and maintained between 70 and 90 g/L) or a liberal strategy to receive red blood cells at 100 g/L (and maintained between 100 and 120 g/L). RESULTS: Baseline characteristics in the restrictive (n = 160) and the liberal group (n = 197) were comparable, except for the use of cardiac and anesthetic drugs (p <.02). Average hemoglobin concentrations (85 +/- 6.2 vs. 103 +/- 6.7 g/L; p <.01) and red blood cell units transfused (2.4 +/- 4.1 vs. 5.2 +/- 5.0 red blood cell units; p <.01) were significantly lower in the restrictive compared with the liberal group. Overall, all mortality rates were similar in both study groups, including 30-day (23% vs. 23%; p = 1.00), 60-day, hospital, and intensive care unit rates. Changes in multiple organ dysfunction from baseline scores were significantly less in the restrictive transfusion group overall (0.2 +/- 4.2 vs. 1.3 +/- 4.4; p =.02). In the 257 patients with severe ischemic heart disease, there were no statistically significant differences in all survival measures, but this is the only subgroup where the restrictive group had lower but nonsignificant absolute survival rates compared with the patients in the liberal group. CONCLUSION: A restrictive red blood cell transfusion strategy generally appears to be safe in most critically ill patients with cardiovascular disease, with the possible exception of patients with acute myocardial infarcts and unstable angina.

Cost comparison of hospital- and home-based treatment models for acute chronic obstructive pulmonary disease.

This trial compared the cost of an integrated home-based care model with traditional inpatient care for acute chronic obstructive pulmonary disease (COPD). 25 patients with acute COPD were randomised to either home or hospital management following request for hospital admission. The acute care at home group costs per separation ($745, CI95% $595-$895, n = 13) were significantly lower (p < 0.01) than the hospital group ($2543, CI95% $1766-$3321, n = 12). There was an improvement in lung function in the hospital-managed group at the Outpatient Department review, decreased anxiety in the Emergency Department in the home-managed group and equal patient satisfaction with care delivery. Acute care at home schemes can substitute for usual hospital care for some patients without adverse effects, and potentially release resources. A funding model that allows adequate resource delivery to the community will be needed if there is a move to devolve acute care to community providers.

Measuring quality of sedation in adult mechanically ventilated critically ill patients. the Vancouver Interaction and Calmness Scale. Sedation Focus Group.

There are no reliable, valid, and responsive scales to measure the quality of sedation in adult critically ill patients. Our objective was to develop a summated rating scale with these properties and to define the minimal clinically important difference (MCID). We developed and tested the scale in an 18-bed medical-surgical intensive care unit (ICU) (12-bed acute and 6-bed subacute unit). Following identification of relevant domains and item derivation, 116 observations were made on 38 patients; psychometric properties and interrater reliability were assessed to allow item reduction. The final scale consisted of two five-item subscales quantifying calmness and interaction along a continuum from 5 to 30 points. Interrater reliability was 0.89 and 0.90; internal consistency was 0. 95 for both subscales. To test construct validity, MCID, and responsiveness 302 observations were made on 54 patients. Construct validity: calmness score vs. need for further intervention to make the patient calm (R = -0.82, P < 0.001); interaction score discriminated between acute vs. subacute units, mean scores 15.28 +/- 8.26 vs. 23.54 +/- 7.42, mean difference 8.27 (95% CI - 10.32 to -6.22); MCID - 2.2 and 2.5 for the calmness and interaction subscales; Guyatt's responsiveness statistics - 1.4 and 2.3. The Vancouver Interaction and Calmness Scale (VICS) is reliable, valid, and responsive.

The ethics of elective (non-therapeutic) ventilation.

Elective ventilation (EV) is ventilation applied, not in the interest of patients, but in order to secure transplantable organs. It carries with it a small risk that patients who would otherwise have died will survive in a persistent vegetative state. Is EV ever justifiable? We argue: (1) The only thing which can justify exposing patients to risk not taken for their benefit is their consent, and we cannot rely on implied consent or third party consent in the case of EV. Thus absent explicit consent of patients, EV is not justifiable. (2) It is not clear that explicit consent should be sought, or where it is offered honoured, given the potential EV has for deterring organ donors and causing stress to staff and families.

A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group.

BACKGROUND: To determine whether a restrictive strategy of red-cell transfusion and a liberal strategy produced equivalent results in critically ill patients, we compared the rates of death from all causes at 30 days and the severity of organ dysfunction. METHODS: We enrolled 838 critically ill patients with euvolemia after initial treatment who had hemoglobin concentrations of less than 9.0 g per deciliter within 72 hours after admission to the intensive care unit and randomly assigned 418 patients to a restrictive strategy of transfusion, in which red cells were transfused if the hemoglobin concentration dropped below 7.0 g per deciliter and hemoglobin concentrations were maintained at 7.0 to 9.0 g per deciliter, and 420 patients to a liberal strategy, in which transfusions were given when the hemoglobin concentration fell below 10.0 g per deciliter and hemoglobin concentrations were maintained at 10.0 to 12.0 g per deciliter. RESULTS: Overall, 30-day mortality was similar in the two groups (18.7 percent vs. 23.3 percent, P= 0.11). However, the rates were significantly lower with the restrictive transfusion strategy among patients who were less acutely ill -- those with an Acute Physiology and Chronic Health Evaluation II score of < or =20 (8.7 percent in the restrictive-strategy group and 16.1 percent in the liberal-strategy group; P=0.03) -- and among patients who were less than 55 years of age (5.7 percent and 13.0 percent, respectively; P=0.02), but not among patients with clinically significant cardiac disease (20.5 percent and 22.9 percent, respectively; P=0.69). The mortality rate during hospitalization was significantly lower in the restrictive-strategy group (22.3 percent vs. 28.1 percent, P=0.05). CONCLUSIONS: A restrictive strategy of red-cell transfusion is at least as effective as and possibly superior to a liberal transfusion strategy in critically ill patients, with the possible exception of patients with acute myocardial infarction and unstable angina.

Variation in red cell transfusion practice in the intensive care unit: a multicentre cohort study.

OBJECTIVES: To determine the degree of interinstitutional transfusion practice variation and reasons why red cells are administered in critically ill patients. STUDY DESIGN: Multicentre cohort study combined with a cross-sectional survey of physicians requesting red cell transfusions for patients in the cohort. STUDY POPULATION: The cohort included 5298 consecutive patients admitted to six tertiary level intensive care units in addition to administering a survey to 223 physicians requesting red cell transfusions in these units. MEASUREMENTS: Haemoglobin concentrations were collected, along with the number and reasons for red cell transfusions plus demographic, diagnostic, disease severity (APACHE II score), intensive care unit (ICU) mortality and lengths of stay in the ICU. RESULTS: Twenty five per cent of the critically ill patients in the cohort study received red cell transfusions. The overall number of transfusions per patient-day in the ICU averaged 0.95 +/- 1.39 and ranged from 0.82 +/- 1.69 to 1.08 +/- 1.27 between institutions (P < 0.001). Independent predictors of transfusion thresholds (pre-transfusion haemoglobin concentrations) included patient age, admission APACHE II score and the institution (P < 0.0001). A very significant institution effect (P < 0.0001) persisted even after multivariate adjustments for age, APACHE II score and within four diagnostic categories (cardiovascular disease, respiratory failure, major surgery and trauma) (P < 0.0001). The evaluation of transfusion practice using the bedside survey documented that 35% (202 of 576) of pre-transfusion haemoglobin concentrations were in the range of 95-105 g/l and 80% of the orders were for two packed cell units. The most frequent reasons for administering red cells were acute bleeding (35%) and the augmentation of O2 delivery (25%). CONCLUSIONS: There is significant institutional variation in critical care transfusion practice, many intensivists adhering to a 100g/l threshold, and opting to administer multiple units despite published guidelines to the contrary. There is a need for prospective studies to define optimal practice in the critically ill.

Diastolic filling in human severe sepsis: an echocardiographic study.

OBJECTIVE: To determine if nonsurvivors have a more abnormal pattern of left ventricular relaxation than survivors with severe sepsis. DESIGN: Prospective, observational, cohort study. SETTING: Intensive care unit in a university-affiliated tertiary care hospital. PATIENTS: Twenty-four adults with severe sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Baseline clinical and hemodynamic variables, Acute Physiology and Chronic Health Evaluation (APACHE) II scores and Doppler echocardiographic mitral inflow pattern (analyzed for normalized peak early filling rate [E/VTI, systolic volumes/sec], deceleration time [msec], and early to atrial filling velocity ratio [E/A]). There were seven deaths. The patients did not differ in baseline demographics, inotropic infusions, hemodynamic measurements or ventilatory settings or variables. Nonsurvivors had a more abnormal pattern of left ventricular relaxation (E/VTI, 4.7 [range 3.8 to 5.8] vs. 5.8 [range 3.8 to 8.9], p= .04; deceleration time, 235 [range 209 to 367] vs. 182 [range 155 to 255], p = .002). E/A showed a nonsignificant trend in the same direction (0.9 [range 0.8 to 1.6] vs. 1.2 [range 0.7 to 1.9], p = .12). In a multivariate analysis, deceleration time (p< .004) and APACHE II score (p < .02) were the only independent predictors of mortality. CONCLUSION: Severe sepsis nonsurvivors have a more abnormal echocardiographic pattern of left ventricular relaxation than survivors.

Admission of bone marrow transplant recipients to the intensive care unit: outcome, survival and prognostic factors.

The role of ICU support in BMT patients is controversial. In an era of constrained resources, the use of prognostic factors predicting outcome may be helpful in identifying patients who are most likely (or unlikely) to benefit from this intervention. We attempted to define the survival of patients admitted to ICU following autologous or allogeneic BMT and to identify those factors important in determining patient outcome. A retrospective study of all adult BMT recipients admitted to intensive care over a 6 year study period was performed to determine overall and prognostic indicators of poor outcome. Pre-treatment, pre-ICU admission and ICU admission data were analyzed to identify factors predicting long-term survival. 116 patients were admitted to ICU on 135 separate occasions with the primary reasons for admission being respiratory failure (66%), sepsis associated with hypotension (10%), and cardiorespiratory failure (8%). No pre-ICU characteristics were predictive of survival. Univariate analysis identified the number of support measures required, the need for ventilation or hemodynamic support, the APACHE II score, the year of ICU admission and the serum bilirubin as significant predictors of post-discharge survival. On multivariate analysis the year of ICU admission, the need for hemodynamic support and the serum bilirubin remained significant. The APACHE II score significantly underestimated survival in the 46% of patients with scores less than 35, and could only be used to predict 100% mortality when it exceeded 45. Twenty-three percent of all BMT patients admitted to the ICU and 17% of ventilated patients survived to hospital discharge. Of the 27 patients surviving to leave hospital, 16 remain alive with a median follow-up of 4.2 years and a mean Karnofsky performance status of 90. Although mortality in BMT recipients admitted to ICU is high our results indicate that intensive care support can be lifesaving and that the outcome in patients requiring ventilation and ICU support may not be as poor as has been previously reported. No single variable was identified which could be used to predict futility but patients requiring both hemodynamic support and mechanical ventilation, and those with an APACHE II score greater than 45 have a very poor prognosis and are unlikely to benefit from lengthy ICU support.

A Canadian survey of transfusion practices in critically ill patients. Transfusion Requirements in Critical Care Investigators and the Canadian Critical Care Trials Group.

OBJECTIVES: To characterize the contemporary red cell transfusion practice in the critically ill and to define clinical factors that influence these practices. DESIGN: Scenario-based national survey. STUDY POPULATION: Canadian critical care practitioners. MEASUREMENTS AND MAIN RESULTS: We evaluated transfusion thresholds before transfusion and the number of red cell units ordered, under the given conditions. Of 254 Canadian critical care physicians, 193 (76%) responded to the survey. The primary specialty of most respondents was internal medicine (56%). Internal medicine respondents were in practice for an average of 8.4 +/- 5.7 (SD) yrs, and worked most often in combined medical/surgical intensive care units. Baseline hemoglobin transfusion thresholds averaged from 8.3 +/- 1.0 g/dL in a scenario involving a young stable trauma victim to 9.5 +/- 1.0 g/dL for an older patient after gastrointestinal bleeding. Transfusion thresholds differed significantly (p< .0001) between all four separate scenarios. With the exception of congestive heart failure (p> .05), all clinical factors (including age, Acute Physiology and Chronic Health Evaluation II score, preoperative status, hypoxemia, shock, lactic acidosis, coronary ischemia, and chronic anemia) significantly (p< .0001) modified the transfusion thresholds. A statistically significant (p< .01) difference in baseline transfusion thresholds was noted across four major regions (with a maximum of five academic centers per region) of the country. Low physician numbers in two of the regions did not allow for further investigation of regional variations. CONCLUSIONS: There is significant variation in critical care transfusion practice, with many intensivists adhering to a 10.0-g/dL threshold, while other physicians described a much more restrictive approach to red cell transfusion. Also, many physicians opted to administer multiple units, despite published guidelines to the contrary. Additionally, the administration of red cells was strongly influenced by a number of clinical factors, many unique to intensive care unit patients. There is a need for prospective studies to define optimal practice in the critically ill.

Does transfusion practice affect mortality in critically ill patients? Transfusion Requirements in Critical Care (TRICC) Investigators and the Canadian Critical Care Trials Group.

In 4,470 critically ill patients, we examined the impact of transfusion practice on mortality rates. As compared with survivors, patients who died in intensive care units (ICU) had lower hemoglobin values (95 +/- 26 versus 104 +/- 23 g/L, p < 0.0001) and were transfused red cells more frequently (42.6% versus 28.0%, p < 0.0001). In patients with cardiac disease, there was a trend toward an increased mortality when hemoglobin values were < 95 g/L (55% versus 42%, p = 0.09) as compared with anemic patients with other diagnoses. Patients with anemia, a high APACHE II score (> 20), and a cardiac diagnosis had a significantly lower mortality rate when given 1 to 3 or 4 to 6 units of allogeneic red cells (55% [no transfusions] versus 35% [1 to 3 units] or 32% [4 to 6 units], respectively, p = 0.01). Adjusted odds ratio (OR) predicting survival were 0.61 (95% CI; 0.37 to 1.00, p = 0.026) after 1 to 3 units and 0.49 (95% CI; 0.23 to 1.03, p = 0.03) after 4 to 6 units compared with nontransfused anemic patients. In the subgroup with cardiac disease, increasing hemoglobin values in anemic patients was associated with improved survival (OR = 0.80 for each 10 g/L increase, p = 0.012). We conclude that anemia increases the risk of death in critically ill patients with cardiac disease. Blood transfusions appear to decrease this risk.

Association of mortality with age of blood transfused in septic ICU patients.

PURPOSE: To determine, retrospectively, the age of packed red blood cell (PRBC) units transfused to patients admitted to the ICU with the diagnosis of severe sepsis and to correlate this variable with outcome. METHODS: All patients admitted to the ICU during 1992 with a diagnosis of severe sepsis were selected retrospectively. The criteria for the diagnosis of severe sepsis and septic shock were based on established guidelines. For each patient the total number of PRBC units transfused, the number of units transfused before, during and after the septic episode, and the age of each PRBC unit transfused were recorded. RESULTS: Of the 31 patients admitted to the ICU with severe sepsis, 19 died and 12 survived. No statistical differences between survivors and nonsurvivors were found with respect to age, sex, number of days in ICU, duration of sepsis, incidence of septic shock, admission Apache II score or total number of PRBC units transfused. During sepsis the median age of PRBC units transfused to survivors was 17 days (range 5-35) vs 25 days (range 9-36) for nonsurvivors (P < 0.0001). A negative correlation (r = -0.73) was found between the proportion of PRBC units of a given age transfused to survivors and increasing age of PRBC. CONCLUSION: This is the first study to report a correlation of mortality with the age of PRBC transfused. The cause of this association is unclear. If this association is confirmed by a prospective randomised trial it would have major implications for the use of PRBC in severe sepsis.

Does increasing oxygen delivery improve outcome in the critically ill? No.

The strategy of treating critically ill patients by increasing oxygen delivery and consumption to values previously observed among survivors of critical illness (supranormal values) is based on the belief that (1) tissue hypoxia may persist in critically ill patients despite aggressive early resuscitation to traditional endpoints of adequate tissue perfusion and (2) that increasing oxygen delivery can reverse tissue hypoxia. This article addresses the question of whether increasing oxygen delivery improves outcomes in critically ill patients by reviewing the relationship between whole-body oxygen delivery and consumption and by critically examining the randomized controlled trials that have increased oxygen delivery to supranormal values.

Transfusion requirements in critical care. A pilot study. Canadian Critical Care Trials Group.

OBJECTIVE: To evaluate the effects of a restrictive and a liberal red blood cell (RBC) transfusion strategy on mortality and morbidity in critically ill patients. STUDY DESIGN: Multicenter, prospective, randomized clinical trial. PATIENT POPULATION: Sixty-nine normovolemic critically ill patients admitted to one of five tertiary level intensive care units with hemoglobin values less than 90 g/L within 72 hours of admission. INTERVENTIONS: Patients were randomly allocated to one of two RBC transfusion strategies. Hemoglobin values were maintained between 100 and 120 g/L in the liberal transfusion group and between 70 and 90 g/L in the restrictive group. RESULTS: Primary diagnosis and mean +/- SD age (58.6 +/- 15 vs 59.0 +/- 21 years and Acute Physiology and Chronic Health Evaluation II score (20 +/- 6.2 vs 21 +/- 7.2) were similar in the restrictive and liberal groups, respectively. Daily hemoglobin values averaged 90 g/L in the restrictive group vs 109 g/L in the liberal group (P < .001). The restrictive group received 2.5 U per patient compared with 4.8 U per patient in the liberal group. This represents a 48% relative decrease (P < .001) in RBC units transfused per patient. The 30-day mortality rate was 24% in the restrictive group compared with 25% in the liberal group; the 95% confidence interval around the absolute difference was -19% to 21%. Similar observations were noted for intensive care unit mortality (P = .76) and 120-day mortality (P > .99). In addition, survival analysis comparing time until death in both groups did not reveal any significant difference (P = .93) between groups. Organ dysfunction scores were also similar (P = .44). CONCLUSION: In this small randomized trial, neither mortality nor the development of organ dysfunction was affected by the transfusion strategy, which suggests that a more restrictive approach to the transfusion of RBCs may be safe in critically ill patients. However, the study lacked power to detect small but clinically significant differences. Therefore, further investigations of RBC transfusion strategies are warranted.

Blood transfusion as a cause of leucocytosis in critically ill patients.

The diagnosis of infection in the intensive care unit is confounded by the presence of non-infectious causes of leucocytosis. Unless such causes are recognised, time and effort will be spent on unnecessary investigations and treatments. In a prospective study we have shown that the transfusion of blood frequently (45/50 patients) causes an acute leucocytosis in such patients. This effect was not seen in 8 patients who received plasma. Blood transfusion should be added to the list of non-infectious causes of leucocytosis in the critically ill.

Identification of the critical oxygen delivery for anaerobic metabolism in critically ill septic and nonseptic humans.

OBJECTIVES: To determine the critical oxygen delivery threshold for anaerobic metabolism and to compare its value between septic and nonseptic critically ill patients. DESIGN: Cohort analytic study, consecutive sample. SETTING: Two tertiary care medical and surgical intensive care units in university hospitals. PATIENTS: Nine septic and nine nonseptic critically ill humans. A diagnosis of sepsis was established by the presence of sepsis syndrome, positive cultures obtained within 48 hours of study, and autopsy evidence of a source of infection. METHODS AND INTERVENTIONS: The O2 consumption (determined by indirect calorimetry), O2 delivery (calculated from the Fick equation), and concentration of arterial plasma lactate were simultaneously determined at 5- to 20-minute intervals while life support was discontinued. MAIN OUTCOME MEASURES: Critical O2 delivery, critical O2 extraction ratio, and maximal O2 extraction ratio. RESULTS: In all septic and eight nonseptic patients, O2 delivery and O2 consumption displayed a biphasic relationship over the range of O2 delivery studied. There were no differences in critical O2 delivery threshold (3.8 +/- 1.5 vs 4.5 +/- 1.3 mL.min-1 x kg-1; P > .28), critical O2 extraction ratio (0.61 +/- 0.05 vs 0.59 +/- 0.16; P > .64), and maximal O2 extraction ratio (0.74 +/- 0.08 vs 0.80 +/- 0.11; P > .29) between septic and nonseptic patients. These data have greater than 90% power to detect a difference of 2 mL.min-1 x kg-1 in the critical O2 delivery and 0.1 in the critical and maximal O2 extraction ratios between the septic and nonseptic groups. CONCLUSIONS: The critical O2 delivery for anaerobic metabolism was identified from the biphasic relationship between O2 delivery and O2 consumption in individual humans. The critical O2 delivery is considerably lower than previously reported in humans with the use of pooled group data. Sepsis does not alter the critical O2 delivery for anaerobic metabolism or tissue O2 extraction ability. Interventions to increase O2 delivery to supranormal levels in critically ill humans in the hope of increasing O2 consumption may be inappropriate.

Merocyanine 540-sensitized photoinactivation of high-grade non-Hodgkin's lymphoma cells: potential application in autologous BMT.

This paper reports on the preclinical evaluation of merocyanine 540 (MC540) as an agent for the inactivation of tumour cells in BM grafts from non-Hodgkin's lymphoma (NHL) patients. The three cell lines used for this study, OCI-LY13.1, OCI-LY13.2 and OCI-LY9, originate from two patients with high-grade NHL. The OCI-LY13.1 and OCI-LY13.2 lines are derived from the same patient. The OCI-LY13.1 line was established at the time of diagnosis while the OCI-LY13.2 line was established after the tumour had become refractory to therapy. When used under conditions that are known to preserve about 50% of normal human pluripotent hematopoietic progenitor cells (CFU-GEMM), MC540-sensitized photoirradiation reduced in vitro clonogenic OCI-LY9 cells by 4 orders of magnitude and OCI-LY13.1 and OCI-LY13.2 cells by > or = 5. Survival curves for OCI-LY13.1 and OCI-LY13.2 cells were similar and followed first order kinetics, while those for OCI-LY9 cells were distinctly biphasic. Suspension cultures established with photoinactivated lymphoma cells confirmed that MC540-sensitized photoirradiation was cytotoxic and capable of eliminating > or = 4 log of tumour cells. These results encourage the further exploration of MC540-sensitized photoirradiation as a means to purge autologous marrow grafts from NHL patients.