Michael G. Mythen

The Effects of Balanced Versus Saline-Based Hetastarch and Crystalloid Solutions on Acid-Base and Electrolyte Status and Gastric Mucosal Perfusion in Elderly Surgical Patients

The IV administration of sodium chloride solutions may produce a metabolic acidosis and gastrointestinal dysfunction. We designed this trial to determine whether, in elderly surgical patients, crystalloid and colloid solutions with a more physiologically balanced electrolyte formulation, such as Hartmann’s solution and Hextend®, can provide a superior metabolic environment and improved indices of organ perfusion when compared with saline-based fluids. Forty-seven elderly patients undergoing major surgery were randomly allocated to one of two study groups. Patients in the Balanced Fluid group received an intraoperative fluid regimen that consisted of Hartmann’s solution and 6% hetastarch in balanced electrolyte and glucose injection (Hextend). Patients in the Saline group were given 0.9% sodium chloride solution and 6% hetastarch in 0.9% sodium chloride solution (Hespan®). Biochemical indices and acid-base balance were determined. Gastric tonometry was used as a reflection of splanchnic perfusion. Postoperative chloride levels demonstrated a larger increase in the Saline group than the Balanced Fluid group (9.8 vs 3.3 mmol/L, P = 0.0001). Postoperative standard base excess showed a larger decline in the Saline group than the Balanced Fluid group (−5.5 vs −0.9 mmol/L, P = 0.0001). Two-thirds of patients in the Saline group, but none in the Balanced Fluid group, developed postoperative hyperchloremic metabolic acidosis (P = 0.0001). Gastric tonometry indicated a larger increase in the CO2 gap during surgery in the Saline group compared with the Balanced Fluid group (1.7 vs 0.9 kPa, P = 0.0394). In this study, the use of balanced crystalloid and colloid solutions in elderly surgical patients prevented the development of hyperchloremic metabolic acidosis and resulted in improved gastric mucosal perfusion when compared with saline-based solutions.

Perioperative fluid management and clinical outcomes in adults

The administration of IV fluid to avoid dehydration, maintain an effective circulating volume, and prevent inadequate tissue perfusion should be considered, along with the maintenance of sleep, pain relief, and muscular relaxation, a core element of the perioperative practice of anesthesia. Knowledge of the effects of different fluids has increased in recent years, and the choice of fluid type in a variety of clinical situations can now be rationally guided by an understanding of the physicochemical and biological properties of the various crystalloid and colloid solutions available. However, there are few useful clinical outcome data to guide this decision. Deciding how much fluid to give has historically been more controversial than choosing which fluid to use. A number of clinical studies support the notion that an approach based on administering fluids to achieve maximal left ventricular stroke volume (while avoiding excess fluid administration and consequent impairment of left ventricular performance) may improve outcomes. In this article, we review the available fluid types and strategies of fluid administration and discuss their relationship to clinical outcomes in adults.

Trial of the Route of Early Nutritional Support in Critically Ill Adults

BACKGROUND Uncertainty exists about the most effective route for delivery of early nutritional support in critically ill adults. We hypothesized that delivery through the parenteral route is superior to that through the enteral route. METHODS We conducted a pragmatic, randomized trial involving adults with an unplanned admission to one of 33 English intensive care units. We randomly assigned patients who could be fed through either the parenteral or the enteral route to a delivery route, with nutritional support initiated within 36 hours after admission and continued for up to 5 days. The primary outcome was all-cause mortality at 30 days. RESULTS We enrolled 2400 patients; 2388 (99.5%) were included in the analysis (1191 in the parenteral group and 1197 in the enteral group). By 30 days, 393 of 1188 patients (33.1%) in the parenteral group and 409 of 1195 patients (34.2%) in the enteral group had died (relative risk in parenteral group, 0.97; 95% confidence interval, 0.86 to 1.08; P=0.57). There were significant reductions in the parenteral group, as compared with the enteral group, in rates of hypoglycemia (44 patients [3.7%] vs. 74 patients [6.2%]; P=0.006) and vomiting (100 patients [8.4%] vs. 194 patients [16.2%]; P<0.001). There were no significant differences between the parenteral group and the enteral group in the mean number of treated infectious complications (0.22 vs. 0.21; P=0.72), 90-day mortality (442 of 1184 patients [37.3%] vs. 464 of 1188 patients [39.1%], P=0.40), in rates of 14 other secondary outcomes, or in rates of adverse events. Caloric intake was similar in the two groups, with the target intake not achieved in most patients. CONCLUSIONS We found no significant difference in 30-day mortality associated with the route of delivery of early nutritional support in critically ill adults. (Funded by the United Kingdom National Institute for Health Research; CALORIES Current Controlled Trials number, ISRCTN17386141.).

Safety of Modern Starches Used During Surgery

Various hydroxyethyl starch (HES) preparations have been used for decades to augment blood volume. There has been concern recently regarding possible adverse outcomes when using HES in the intensive care setting, especially in patients with septic shock. However, the pharmacokinetic and pharmacodynamic properties of HES preparations depend on their chemical composition and source material. Thus, different clinical conditions could result in differing effectiveness and safety for these preparations. Consequently, we assessed the safety of tetrastarches when used during surgery, using a formal search, that yielded 59 primary full publications of studies that met a priori inclusion criteria and randomly allocated 4529 patients with 2139 patients treated with tetrastarch compared with 2390 patients treated with a comparator. There were no indications that the use of tetrastarches during surgery induces adverse renal effects as assessed by change or absolute concentrations of serum creatinine or need for renal replacement therapy (39 trials, 3389 patients), increased blood loss (38 trials, 3280 patients), allogeneic erythrocyte transfusion (20 trials, 2151 patients; odds ratio for HES transfusion 0.73 [95% confidence interval = 0.61–0.87], P = 0.0005), or increased mortality (odds ratio for HES mortality = 0.51 [0.24–1.05], P = 0.079).

Risk stratification tools for predicting morbidity and mortality in adult patients undergoing major surgery: qualitative systematic review.

Risk stratification is essential for both clinical risk prediction and comparative audit. There are a variety of risk stratification tools available for use in major noncardiac surgery, but their discrimination and calibration have not previously been systematically reviewed in heterogeneous patient cohorts.Embase, MEDLINE, and Web of Science were searched for studies published between January 1, 1980 and August 6, 2011 in adult patients undergoing major noncardiac, nonneurological surgery. Twenty-seven studies evaluating 34 risk stratification tools were identified which met inclusion criteria. The Portsmouth-Physiology and Operative Severity Score for the enUmeration of Mortality and the Surgical Risk Scale were demonstrated to be the most consistently accurate tools that have been validated in multiple studies; however, both have limitations. Future work should focus on further evaluation of these and other parsimonious risk predictors, including validation in international cohorts. There is also a need for studies examining the impact that the use of these tools has on clinical decision making and patient outcome.

A Head-to-Head Comparison of the In Vitro Coagulation Effects of Saline-Based and Balanced Electrolyte Crystalloid and Colloid Intravenous Fluids

Both fluid composition (e.g., type of hydroxyethyl starch) and formulation (e.g., saline or balanced salt carrier solution) may alter whole blood coagulation. We therefore enrolled 10 healthy volunteers to test ex vivo, thrombelastograph®-based blood coagulation differences of eight crystalloid and colloid solutions at 20%, 40%, and 60% dilutions. Saline and lactated Ringers solution produced a hypercoagulable state at 20%–40% dilutions. Saline, hetastarch in saline, pentastarch in saline, tetrastarch in saline, and human albumin solutions all produced a hypocoagulable state at 60% dilution. Hetastarch in saline also produced a hypocoagulable state at 40% dilution. The larger molecular weight starches produced more intense coagulation abnormalities than the medium molecular weight compounds formulated similarly (i.e., suspended in saline or balanced salt solution). The balanced salt solutions caused fewer coagulation abnormalities, especially pentastarch in balanced salt solution. This balanced salt pentastarch preparation produced the least derangement of coagulation of the colloid solutions at all dilutions, causing hypercoagulability at the lower dilutions and minimal coagulation derangement at 60% dilution. These data support the theory that smaller molecular weight hydroxyethyl starches and colloids suspended in balanced salt solutions preserve coagulation better than large molecular weight starches and saline-based colloids, as judged by thrombelastography.

Postoperative gastrointestinal tract dysfunction.

Postoperative gastrointestinal (GI) tract dysfunction (PGID) is common and is associated with increased patient suffering and cost of care. The pathogenesis of PGID is complex and multifactorial. Traditional measures intended to reduce the incidence of PGID, such as the use of prokinetic drugs, nasogastric tube drainage, and the avoidance of early fluid and/or food intake, are apparently not beneficial. The administration of larger volumes of IV fluids to achieve predetermined increases in cardiac output has been shown in randomized trials to improve gut perfusion and reduce the incidence of PGID. A multimodal approach that includes limited surgical incision, regional local anesthesia, early mobilization, and enteral feeding has been associated with a dramatic reduction in postoperative complications, PGID, and length of hospital stay. However, none of these approaches has been validated in adequately powered multicenter prospective randomized controlled trials.

Automated detection of gastric luminal partial pressure of carbon dioxide during cardiovascular surgery using the Tonocap.

Background A new automated system of air tonometry (Tonocap; Datex Ohmeda, Helsinki, Finland) allows for frequent (every 15 min) measurement of gastric luminal partial pressure of carbon dioxide. Its use has not been described in cardiac surgical patients. Methods One hundred patients undergoing coronary artery bypass graft or cardiac valve surgery were enrolled in a prospective cohort study. After anesthetic induction and insertion of a TRIP NGS Catheter (Datex Ohmeda), measurements of gastric luminal partial pressure of carbon dioxide were obtained using the Tonocap, and gastric mucosal p H (p Hi) was calculated. The main outcome measure was postoperative complication, defined as either in-hospital death or prolonged postoperative hospitalization (> 14 days). Results Four patients (4%) died, all of multiple-system organ failure, one each on postoperative days 9, 26, 46, and 121. Postoperative complication occurred in 18 patients (18%), all of whom exhibited persistent dysfunction of at least one organ system. Perioperatively, an abnormal p Hi (< 7.32) and gastric luminal minus arterial partial pressure of carbon dioxide gap (> 8 mmHg) occurred in 66% and 70% of patients, respectively. Predictors of postoperative complication included postoperative pHi (P = 0.001), gastric luminal partial pressure of carbon dioxide (P = 0.022), and gastric luminal minus arterial partial pressure of carbon dioxide gap (P = 0.013). In contrast, arterial base excess (P > 0.4) and routinely measured hemodynamic variables (e.g., heart rate, blood pressure) were either less predictive compared with Tonocap-derived variables or not predictive. Conclusions Despite a low mortality rate, patients undergoing cardiac surgery exhibited high incidences of prolonged hospitalization and postoperative morbidity. The Tonocap was easy to use, particularly compared with saline tonometry. Several Tonocap-derived variables were predictive of postoperative complications consistent with previously published data using saline tonometry.

Hydroxyethyl Starch in Balanced Electrolyte Solution (Hextend ® )—Pharmacokinetic and Pharmacodynamic Profiles in Healthy Volunteers

Hextend® is a new plasma volume expander containing 6% hydroxyethyl starch (HES) in a physiologically balanced medium of electrolytes, glucose, and lactate (weight average, molecular weight 670 kDa, molar substitution 0.75). This open-label study was designed to investigate the pharmacokinetic and pharmacodynamic profiles of Hextend® in 21 healthy volunteers. We infused Hextend® 10 ml/kg IV over 20 min and determined serum concentrations of HES at selected intervals over a 7-day period. Serum concentration-time curves indicated mixed pharmacokinetic behavior reflecting a two-compartment model in most subjects. The median serum half-life over 7 days was 38.2 h. The balanced formulation of the suspension medium did not seem to affect distribution, metabolism, or excretion of Hextend® when compared with similar HES. Pharmacodynamic analysis demonstrated decreases in some plasma components compatible with the infusion of that volume of fluid and the duration of plasma volume expansion. Other plasma components remained unchanged, reflecting the benefit of a balanced electrolyte solution. Hemodilution was observed for 24–48 h after short-term infusion of Hextend®. Some hemostatic indices showed moderate changes, and serum amylase demonstrated a temporary increase. Our study suggested that Hextend® has pharmacokinetic and pharmacodynamic profiles that are similar to those of other HES.

The association of complication type with mortality and prolonged stay after cardiac surgery with cardiopulmonary bypass.

Outcome after cardiac surgery varies depending on complication type. We therefore sought to determine the association between complication type, mortality, and length of stay in a large series of patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Multivariate logistic regression was used to test for differences between complication types in mortality and prolonged length of stay (>10 days) while controlling for preoperative and intraoperative risk factors. In 2609 consecutive cardiac surgical patients requiring CPB, the mortality rate was 3.6%; 36.5% had one or more complications, and 15.7% experienced an adverse outcome (death or prolonged length of stay). Multivariate logistic regression demonstrated that complication type was significantly associated with adverse outcome (P < 0.001) independent of Parsonnet score and CPB time (c-index = 0.80). The development of noncardiac complications only (Group NC) and cardiac complications with other organ involvement (Group B) significantly increased mortality and hospital and intensive care unit length of stay (P < 0.001) when compared with cardiac complications only (Group C). The incidences of adverse outcome in Groups C, NC, and B were 15%, 43%, and 67%, respectively; the mortality rates were 3%, 7%, and 20%, respectively. All these intergroup comparisons were significantly different (adjusted P < 0.05). Complications involving organs other than the heart appear to be more deleterious than cardiac complications alone, underscoring the need for strategies to reduce noncardiac complications.