Outcome prediction in cardiac surgery: the first logistic scoring model for cardiac surgical intensive care patients.

BACKGROUND: In the process of risk stratification, a logistic calculation of mortality risk in percentage is easier to interpret. Unfortunately, there is no reliable logistic model available for postoperative intensive care patients. The aim of this study was to present the first logistic model for postoperative mortality risk stratification in cardiac surgical intensive care units. This logistic version is based on our previously presented and established additive model (CASUS) that proved a very high reliability. METHODS: In this prospective study, data from all adult patients admitted to our ICU after cardiac surgery over a period of three years (2007-2009) were collected. The Log-CASUS was developed by weighting the 10 variables of the additive CASUS and adding the number of postoperative day to the model. Risk of mortality is predicted with a logistic regression equation. Statistical performance of the two scores was assessed using calibration (observed/expected mortality ratio), discrimination (area under the receiver operating characteristic curve), and overall correct classification analyses. The outcome measure was ICU mortality. RESULTS: A total of 4054 adult cardiac surgical patients was admitted to the ICU after cardiac surgery during the study period. The ICU mortality rate was 5.8%. The discriminatory power was very high for both additive (0.865-0.966) and logistic (0.874-0.963) models. The logistic model calibrated well from the first until the 13th postoperative day (0.997-1.002), but the additive model over- or underestimated mortality risk (0.626-1.193). CONCLUSION: The logistic model shows statistical superiority. Because of the precise weighing the individual risk factors, it offers a reliable risk prediction. It is easier to interpret and to facilitate the integration of mortality risk stratification into the daily management more than the additive one.

Esophagogastrectomy for benign esophageal stricture. Fate of the esophagogastric anastomosis.

Eighty-nine patients who had resection of benign esophageal stricture with esophagogastrostomy were reviewed through medical records and by mailed questionnaire. The 30-day mortality rate was 8.9%. Seventy-six patients were available for follow-up for an average of 66.4 months (Group 1). Forty-three of these patients were followed up for longer than 5 years (Group 2). The incidence of postoperative heartburn in Groups 1 and 2 was 7.9% and 7.0%, respectively. The incidence of postoperative dysphagia in Groups 1 and 2 was 39.4% and 30.2%, respectively, with most episodes occurring within 2 years of operation. The vast majority of these patients required multiple esophageal dilatations over a long time. The high rate of restricture precludes support for the routine use of an esophagogastric anastomosis after resection of benign esophageal stricture.

Prevention of alterations in postoperative lymphocyte subpopulations by cimetidine and ibuprofen.

Surgical procedures probably result in a temporary state of immunosuppression. Identification of functional lymphocyte subclasses using appropriate monoclonal antibodies appears to serve as a sensitive, accurate, and reproducible measure of immune status in patients in many disease states. Using monoclonal antibodies specific for lymphocyte surface markers and immunofluorescent assay, we quantitated lymphocyte subpopulations in patients undergoing surgical procedures. Cholecystectomy, colon surgery, and coronary bypass procedures all resulted in postoperative decreases in helper and inducer populations and increases in cytotoxic suppressor populations, with resultant depressions in the helper to suppressor lymphocyte ratio. Studies in an additional group of patients who underwent cholecystectomy demonstrated that these changes could be prevented by perioperative administration of ibuprofen and cimetidine. These results suggest that prostaglandins and histamines are involved in immunoregulatory events after major operation. The ability of specific pharmacologic therapy to prevent alterations in lymphocyte populations suggest that postoperative immunity may be preserved, hopefully leading to greater host resistance against infection and tumor dissemination.

Postburn immunosuppression in an animal model. IV. Improved resistance to septic challenge with immunomodulating drugs.

We have previously demonstrated that certain pharmacologic agents administered to burned mice will restore cell-mediated immunity, as evidenced by measurement of delayed hypersensitivity responses and determination of splenic helper/suppressor lymphocyte ratios. These drugs are systemic cimetidine, ibuprofen, cyclophosphamide, and topical cerium nitrate. In the studies reported here we performed cecal ligation and puncture (CLP) in burned mice as a measure of resistance to infectious challenge. Survival after CLP with a 23-gauge needle used for puncture was markedly decreased when performed on the tenth postburn day (normal 63.7%, 10 days postburn 20.0%; p less than 0.001), but survival was not decreased when CLP was performed on the fifth (60.0%; p not significant) or twenty-first postburn day (65.3%; p not significant). Animals were then treated with the four agents in carefully defined dosage regimens, and survival was again determined on the tenth postburn day. Survival figures with p values compared to burned, untreated animals: burn plus cimetidine 62.2%, p less than 0.0005; burn plus: ibuprofen 64.7% p less than 0.0003; burn plus cyclophosphamide 68.2%, p less than 0.0001; burn plus cerium nitrate 54.1%, p less than 0.004. Specific pharmacologic therapy in burned mice in dosage regimens that have been shown to improve cell-mediated immunity is also able to significantly improve resistance to subsequent infectious challenge.

Prevention of suppressed cell-mediated immunity in burned mice with histamine-2 receptor antagonist drugs.

Thermal injury has been shown to suppress many aspects of both specific and nonspecific immune responses. We investigated the effect of two histamine H-2 antagonist drugs on cell-mediated immunity in burned mice, utilizing a method of quantitating the degree of contact sensitivity elicited to the antigen. 2,4-dinitrofluorobenzene (DNFB). Following sensitization by painting the abdomen with DNFB, animals were challenged 5 days later by painting the ears; subsequent ear swelling is a sensitive and reproducible measure of cell-mediated immunity. We have previously demonstrated that burned mice are maximally immunosuppressed 10 to 14 days following burn injury. In the present study we found that daily intraperitoneal administration of appropriate doses of the H-2 antagonists cimetidine (2 and 10 mg/kg/day) and ranitidine (2 and 10 mg/kg/day) resulted in maintenance of normal cell-mediated immunity in burned animals. Neither a lower dose of ranitidine (0.2 mg/kg/day) nor higher doses of cimetidine (20 and 50 mg/kg/day) restored immunity, and diphenhydramine, an H-1 antagonist, had no effect. There was no augmentation of contact sensitivity in unburned mice treated with cimetidine. The immunorestorative effect is probably secondary to antagonism of histamine H-2 receptors on suppressor T lymphocytes, and may reflect increased suppressor cell activity in burned mice; however, other mechanisms may be involved.

The effect of histamine receptor antagonists on specific and nonspecific suppression of experimental contact sensitivity.

We studied the effects of H1 and H2 histamine receptor antagonists on down regulation of contact sensitivity (CS) to dinitrofluorobenzene (DNFB). Two H2 receptor antagonists, cimetidine and ranitidine, reversed the nonspecific immunosuppression of CS induced by burns. On the other hand, these two drugs did not affect the antigen-specific suppressor T cell-mediated tolerance to DNFB induced by dinitrobenzene sulfonic acid. Two H1 antagonists did not affect the down regulation of CS induced by either tolerance or burning. The differential sensitivities to histamine 2-receptor antagonists indicate that the mechanisms for nonspecific burn-induced immunosuppression are different from those for hapten-specific tolerance to DNFB.

Restoration of immunity in burned mice by cimetidine.

We have previously described a mouse model of postburn suppression of cell-mediated immunity (CMI). Ear swelling (ES) in response to contact antigen challenge is depressed maximally 14 days following a 25% steam burn and recovers to control levels 3 weeks postburn. Splenic lymphocyte proliferation in response to Concanavalin A (Con A) is also depressed 14 days postburn. Splenic T-lymphocyte subset analysis with monoclonal antibodies for helper cells (Lyt 1.2) and suppressor cells (Lyt 2.2) reveals that T-helper cells reach a minimal level and T suppressor cells reach a maximum level 14 days postburn. The helper: suppressor ratio (HSR) reaches its nadir at day 14. Treatment of burned mice with low-dose cimetidine (2 or 10 mg/kg/day), but not high-dose (50 mg/kg/day), for 14 days restores CMI. Low-dose cimetidine also normalizes the HSR but does not effect postburn depression of mitogen responsiveness. Low-dose cimetidine probably restores CMI by inhibiting suppressor cells, whereas high doses provide more global inhibition. Recovery of mitogen responsiveness may require continued cimetidine presence in culture.

Altered helper and suppressor lymphocyte populations in surgical patients. A measure of postoperative immunosuppression.

Although a wealth of evidence has suggested that cell-mediated immunity is suppressed after simple surgical trauma, there have been contradictory results using stimulation assays of lymphocyte function. We quantitated T-lymphocyte subsets in 11 patients undergoing routine cholecystectomy by immunofluorescence microscopy using specific monoclonal antibodies. T-helper to T-suppressor cell ratios were calculated on the preoperative day and the first postoperative day in all patients, and on the third or fourth postoperative day in five patients. Helper to suppressor ratios decreased in all patients on the first postoperative day (p greater than 0.01), but returned to within normal limits on subsequent days. Changes were due more to decreases in helper cells than to increases in suppressor cells, although changes in both populations were statistically significant. The measurement of T-cell subsets by antibody-specific labeling and immunofluorescence microscopy may prove to be a more sensitive, quantifiable, and reproducible assay of immune function in surgical or traumatized patients than use of stimulation assays. Measurements of specific helper and suppressor lymphocyte populations may prove useful in predicting morbidity and mortality, and may also help in studying the effect of immunomodulating agents on the immune response.