(1) Background: In critically ill cardiac patients, parenteral and enteral food and drug administration routes may be used. However, it is not well known how drug absorption and metabolism are altered in this group of adult patients. Here, we analyze drug absorption and metabolism in patients after cardiogenic shock using the pharmacokinetics of therapeutically indicated esomeprazole. (2) Methods: The pharmacokinetics of esomeprazole were analyzed in a consecutive series of patients with cardiogenic shock and controls before and after elective cardiac surgery. Esomeprazole was administered orally or with a nasogastric tube and once as an intravenous infusion. (3) Results: The maximum plasma concentration and AUC of esomeprazole were, on average, only half in critically ill patients compared with controls (p < 0.005) and remained lower even seven days later. Interestingly, esomeprazole absorption was also markedly compromised on day 1 after elective surgery. The metabolites of esomeprazole showed a high variability between patients. The esomeprazole sulfone/esomeprazole ratio reflecting CYP3A4 activity was significantly lower in critically ill patients even up to day 7, and this ratio was negatively correlated with CRP values (p = 0.002). The 5'-OH-esomeprazole and 5-O-desmethyl-esomeprazol ratios reflecting CYP2C19 activity did not differ significantly between critically ill and control patients. (4) Conclusions: Gastrointestinal drug absorption can be significantly reduced in critically ill cardiac patients compared with elective patients with stable cardiovascular disease. The decrease in bioavailability indicates that, under these conditions, any vital medication should be administered intravenously to maintain high levels of medications. After shock, hepatic metabolism via the CYP3A4 enzyme may be reduced.

Altered drug and nutrient absorption presents a unique challenge in critically ill patients. Performing an acetaminophen absorption test (AAT) has been used as a marker for gastric motility and upper small bowel absorption; thus, it may provide objective data regarding enteral absorptive ability in critically ill patients.

What is the clinical experience with AAT when used as a surrogate marker for enteral absorption in critically ill patients?

This single-center, retrospective, cohort study evaluated serum acetaminophen concentrations within 180 minutes following 1-time enteral administration of an AAT. Patients admitted to the surgical and medical intensive care units and medical intensive care units over a 7-year period were evaluated. Groups were defined as positive (acetaminophen concentration of ≥10 mg/L) or negative (acetaminophen concentration of <10 mg/L) AAT.

The outcomes were to describe the clinical experience, characteristics, and performance of AAT.

Forty-eight patients were included. Patients were 58.5 ± 14 years of age, mostly male (58.3%), and admitted to the surgical intensive care unit (66.7%). Median hospital length of stay was 47.5 (27-78.8) days. Thirty-four patients (70.8%) had a positive AAT [median concentration, 14 (12-18) mg/L]. Median time to first detectable concentration was 37 (33-64) minutes. AAT characteristics were similar between the groups including total dose, weight-based dose, time to first and second assays, drug formulation, and site of administration between groups. There were no independent risk factors identified on regression analysis for negative AAT.

An acetaminophen dose of 15 mg/kg with 2 coordinated serum concentrations approximately 30 and 60 minutes after administration is a reasonable construct for AAT. Future research is needed to assess AAT utility, safety, and clinical outcomes for predicting patient ability to absorb enteral feeds and medications.

The correlation between gastric residual volumes (GRV) and markers of gastric emptying (GE) in critically ill patients is unclear. This is especially true for ICU surgical patients as they are underrepresented in previous studies.

We conducted a post-hoc analysis of a multicenter trial that investigated the effectiveness of a promotility drug in increasing enteral nutrition intake. Pharmacokinetic markers of GE [3-O-methylglucose (3-OMG) and acetaminophen] were correlated with GRV measurements. High-GRV was defined as one episode of >400 mL or two consecutive episodes of >250 mL, and delayed GE was defined as <20^th percentile of the pharmacokinetic GE marker that had the strongest correlation with GE.

Out of 77 patients, 8 (10.4%) had high-GRV, and 15 (19.5%) had delayed GE. 3-OMG concentration at 60 mins had the strongest correlation with GRV (Rho: - 0.631), and high-GRV had low sensitivity (46.7%) but high specificity (98.4%) in discriminating delayed GE. The positive (87.5%) and negative (88.4%) predictive values were similar. There was a small sample of surgical patients (n = 14, 18.2%), and they had a significantly higher incidence of high-GRV (29% vs 6%, P: 0.032) and a trend towards delayed GE (36% vs 16%, p: 0.132) when compared to medical patients.

GRV reflects GE, and high-GRV is an acceptable surrogate marker of delayed GE. Based on our preliminary observation, surgical patients may have a higher risk of high-GRV and delayed GE. In summary, GRV should be monitored to determine if complex investigations or therapeutic interventions are warranted. This article is protected by copyright. All rights reserved.

Cardiac surgery is performed more often in a population with an increasing number of comorbidities. Although these surgeries can be lifesaving, they disturb homeostasis and may induce a temporary overall loss of physiologic function. The required postoperative intensive care unit and hospital stay often lead to a mid- to long-term decline of nutritional and physical status, mental health, and health-related quality of life. Prehabilitation before elective surgery might be an opportunity to optimize the state of the patient. This article discusses current evidence and potential effects of preoperative optimization of nutrition and physical status before cardiac surgery.

To compare the outcomes of hysterectomy patients who received standard pain management including IV acetaminophen (IV APAP) versus oral APAP.

We performed a retrospective analysis of the Premier Database (January 2012 to September 2015) comparing hysterectomy patients who received postoperative pain management including IV APAP to those who received oral APAP starting on the day of surgery and continuing up to the third post-operative day, with no exclusions based on additional pain management. We compared the groups on length of stay (LOS), hospitalization costs, and average daily morphine equivalent dose (MED). The quarterly rate of IV APAP use for all hospitalizations by hospital was used as an instrumental variable in two-stage least squares regressions also adjusting for patient demographics, clinical risk factors, and hospital characteristics.

We identified 22,828 hysterectomy patients including 14,811 (65%) who had received IV APAP. Study subjects averaged 50 and 52 years of age, respectively in the IV APAP and oral APAP cohorts and were predominantly non-Hispanic Caucasians (≥60% in both cohorts). Instrumental variable models found IV APAP associated with 0.8 days shorter hospitalization (95% CI: -0.92 to -0.68, p<0.0001) and $2,449 lower hospitalization costs (95% CI: -$2,902 to -$1,996, p<0.0001). Average daily MED trended lower without statistical significance (-1.41 mg, 95% CI: -3.43 mg to 0.61 mg, p = 0.17).

Compared to oral APAP, managing post-hysterectomy pain with IV APAP is associated with shorter LOS and lower total hospitalization costs.

The pleiotropic biochemical and antioxidant functions of vitamin C have sparked recent interest in its application in intensive care. Vitamin C protects important organ systems (cardiovascular, neurologic and renal systems) during inflammation and oxidative stress. It also influences coagulation and inflammation; its application might prevent organ damage. The current evidence of vitamin C's effect on pathophysiological reactions during various acute stress events (such as sepsis, shock, trauma, burn and ischemia-reperfusion injury) questions whether the application of vitamin C might be especially beneficial for cardiac surgery patients who are routinely exposed to ischemia/reperfusion and subsequent inflammation, systematically affecting different organ systems. This review covers current knowledge about the role of vitamin C in cardiac surgery patients with focus on its influence on organ dysfunctions. The relationships between vitamin C and clinical health outcomes are reviewed with special emphasis on its application in cardiac surgery. Additionally, this review pragmatically discusses evidence on the administration of vitamin C in every day clinical practice, tackling the issues of safety, monitoring, dosage, and appropriate application strategy.

The authors hypothesized that intravenous acetaminophen as an adjunct analgesic would significantly decrease 24-hour postoperative opioid consumption.

Double-blind, randomized, placebo-controlled trial.

A single academic medical center.

The study was comprised of 68 adult patients undergoing cardiac surgery.

Patients were assigned randomly to receive either 1,000 mg of intravenous acetaminophen or placebo immediately after anesthesia induction, at the end of surgery, and then every 6 hours for the first 24 hours in the intensive care unit, for a total of 6-1,000 mg doses.

The primary outcome was 24-hour postoperative opioid consumption. The secondary outcomes included 48-hour postoperative opioid consumption, incisional pain scores, opioid-related adverse effects, length of mechanical ventilation, length of intensive care unit stay, and the extent of wound hyperalgesia assessed at 24 and 48 hours postoperatively. The mean±standard deviation postoperative 24-hour opioid consumption expressed in morphine equivalents was significantly less in the acetaminophen group (45.6±29.5 mg) than in the placebo group (62.3±29.5 mg), representing a 27% reduction in opioid consumption (95% CI, 2.3-31.1 mg; p = 0.024). There were no differences in pain scores and opioid-related adverse effects between the 2 groups. A significantly greater number of patients in the acetaminophen group responded "very much" and "extremely well" when asked how their overall pain experience met their expectation (p = 0.038).

The administration of intravenous acetaminophen during cardiac surgery and for the first 24 hours postoperatively reduced opioid consumption and improved patient satisfaction with their overall pain experience but did not reduce opioid side effects.

Critically ill patients may experience delayed gastric emptying. Patients receiving enteral feeding are monitored closely to detect a delay of gastric emptying, assess feeding tolerance, and prevent aspiration pneumonia. The most common practice for assessing gastric emptying is to measure the aspirated gastric residual volume; however, this is an unreliable method that lacks standardization, fails to differentiate normal digestive secretions from enteral formula, and results in unnecessary interruptions of enteral nutrition. The aim of this review is to identify an alternative method to assess gastric emptying, which should be reliable, sensitive, harmless, feasible, and inexpensive. Several techniques are discussed: scintigraphy, paracetamol absorption test, breath tests, refractometry, ultrasound, and gastric impedance monitoring. Refractometry seems to be the most appropriate tool for the regular assessment of enteral nutrition; however, standardization and validation of this method are needed before it can be routinely used to monitor critically ill patients receiving enteral nutrition.

beta-adrenoceptor antagonists, especially atenolol, reduce perioperative cardiac morbidity. Because there are no data on the bioavailability of atenolol given by nasogastric tube in the postoperative period, we assessed the efficacy of this route of administration in 18 patients scheduled for abdominal surgery. We found a 36% reduction in the area under the atenolol concentration curve and a 46% reduction in the peak concentration of atenolol in the postoperative period compared with preoperative values. In addition, patients had more rapid mean heart rates on the second postoperative day compared with the day before surgery. We conclude that the administration of atenolol via nasogastric tube in the postoperative period does not result in adequate plasma concentrations.

Enteral feeding is the preferred method of nutritional support in the critically ill; however, evidence suggests that many critically ill patients do not meet their nutritional goals. The implementation of enteral feeding protocols has improved nutritional delivery, although protocols can be widely variable. Similarly, enteral feeding related nursing practice is also inconsistent within and between intensive care units (ICUs). These variations in enteral feeding practice can be linked to the shortage of reliable and valid research into the many issues associated with the effective delivery of enteral nutrition. In the absence of a strong research tradition and practice, rituals are embraced and rarely challenged, further contributing to the wide variations in enteral feeding practice. Of particular importance are practice issues related to the commencement of enteral feeding and the assessment of feeding tolerance. This article seeks to review the literature related to commencing enteral feeding, with particular reference to the suitability of enteral nutrition, methods of enteral feeding and adjustment of enteral feeding rates. Issues relating to feeding intolerance, including the assessment of gastric residual volume and the development of diarrhoea, will also be explored.

Early enteral nutrition (EN) improves intestinal integrity, motility and immunocompetence. However, technical problems such as diarrhoea and gastric residual volumes are said to be associated with the method and have prevented its implementation. We have prospectively assessed clinical problems connected to early EN.

Seventy-three consecutive patients eligible for EN were assessed and observed until discharge from the intensive care unit (ICU) or until they resumed oral nutrition. They had surgery for coronary artery bypass grafting and/or valvular disease, thoracic or thoracoabdominal aortic aneurysms or other combined procedures. Two cardiac patients were not subjected to surgery.

In 59/73 patients, EN was started within 3 days. EN was discontinued in half of the patients when they were able to feed themselves. Twelve patients vomited, one of them severely. Dislocation of the nasogastric tube occurred in 28 patients. The 15 patients with diarrhoea were treated with 2-6 broad-spectrum antibiotics during their ICU-stay. Out of 73, 40 patients did not show any gastric residual volume (GRV). GRV decreased during EN in 50% of the patients with fairly large or large residual volumes. The incidence of aspiration pneumonia was 10%.

In the cardiothoracic ICU, individually adjusted early EN is feasible with few problems.

We designed this study to assess intestinal absorption in patients with adequate or altered hemodynamic status after cardiac surgery and to test clinical tolerance to early enteral nutrition.

Prospective, descriptive study.

Surgical intensive unit in a university teaching hospital.

Cardiac surgery patients, age 64+/-10 yrs (mean +/-SD) were subdivided into two groups according to hemodynamic status: group I, 16 patients with adequate hemodynamic status; group II, 23 patients with hemodynamic failure. These groups were compared with healthy controls (group III, n = 6).

Paracetamol pharmacokinetic study on days 1 and 3 with nasogastric or postpyloric paracetamol administration. Early postpyloric or conventional gastric nutrition in group II.

Plasma concentrations were measured on days 1 and 3, and area under the curve (AUC) was calculated. Absorption was strongly reduced on day 1 in all patients after gastric administration (lower peak paracetamol and AUC), but normal after postpyloric delivery. Duration of anesthesia and of circulatory bypass did not affect paracetamol absorption. On day 3, AUC was close to normal in case of hemodynamic failure. Peak absorption on day 1 was negatively correlated with opiate dose (r2 = 0.176, p = .008). Hypocaloric enteral nutrition was well tolerated.

The close-to-normal AUC, during low cardiac output, despite lower peak paracetamol, shows absorption was not suppressed, only delayed, because of decreased pyloric motility. The decrease on day 1 can be attributed to opiates, known to alter pyloric function and to slow down the intestinal transit.

The purpose of this study was to investigate the effect of a relatively novel technology, functional magnetic stimulation (FMS), on gastrointestinal transit of liquids in rats. Orogastric gavage with technetium-99 solution was used to assess gastric emptying and gastrointestinal transit time in 92 rats. FMS was performed over the anterior cervical and/or dorsal thoracolumbar regions using a figure-8 coil. Stimulation protocols were 1, 2, or 4 h in length. FMS accelerated gastric emptying and decreased gastrointestinal transit time. The acceleration was dependent on the stimulation parameters used as well as on the duration of the protocol; high levels of FMS produced a quicker effect, whereas lower levels were effective at later times. This study provides evidence that FMS could be an alternative or adjunct therapy to treat disorders in gastrointestinal motility.

The pharmacokinetics of paracetamol in adults after cardiac surgery have not been described. Twenty patients were randomized to receive either paracetamol 2 g through a nasogastric tube and as a suppository eight hours later or vice versa. Arterial blood samples were taken at 0.5, one, two, four, six and eight hours after dosing. Each patient was studied for 16 h. There were 16 males and three females. One patient was excluded because of sampling errors. The mean age was 59 (SD 8) years and the mean weight 84 kg (16). The time-concentration profiles for each individual were used to estimate pharmacokinetic parameters using a non-linear mixed effects model (NONMEM). Population parameter estimates with coefficient of variation (CV%), standardized to a 70 kg person, for a one-compartment model with first order input, lag time and first order elimination were volume of distribution 127l (28) and clearance 26.4 l/h (29) Rectal paracetamol had an absorption half-life (Tabs) of 2.02 h (31) with a lag time of 0.28 h. The absorption half-life for the oral preparation was 1.49 h (81) with a lag time of 0.17 h. The relative bioavailability of the rectal compared to the oral formulation was 0.98 (18). Concentrations after either nasogastric or rectal paracetamol 2 g were below a target concentration of 10 mg/l, which is associated with analgesia. Absorption after nasogastric administration was slow compared to healthy adults (Tabs 0.06 to 0.7 h) and the bioavailability was half that expected, due to nasogastric loss. Parameter estimates had large variability. Paracetamol is unlikely to have useful clinical impact in the majority of patients when standard doses (6 g/day) are given on day 1 after cardiac surgery.

To investigate the absorption of the gastrokinetic drug, cisapride, and effect of cisapride on gastric emptying in critically ill patients; and to assess the usefulness of clinical signs of gastric emptying.

Prospective, randomized, controlled study.

Medical/surgical/trauma intensive care unit (ICU) in a university hospital.

Twenty-seven consecutively enrolled patients, aged 18 to 65 yrs, with normal hepatic and renal biochemistry who were not receiving enteral nutrition and who had no contraindications to enteral nutrition. These patients were expected to stay in the ICU for at least 4 days.

Patients were randomized to receive either placebo or rectal cisapride, 60 mg initially followed by two doses of 30 mg at 8-hr intervals.

Gastric emptying was estimated, using acetaminophen absorption on day 1 of the study. Placebo or cisapride was administered and a second acetaminophen absorption test for gastric emptying was carried out on day 2,24 hrs after the first test. Four patients were excluded because of incomplete data. Statistical analysis was performed, using the area under the acetaminophen absorption curve from 0 to 60 mins as the primary measure of gastric emptying. There was no significant change in the area under the acetaminophen absorption curve from 0 to 60 mins from day 1 to day 2 in patients who received placebo or cisapride. Using the combination of the time to maximum acetaminophen concentration (< or = 30 mins) with a maximum concentration (> 12 mg/L) to define "normal" emptying, on day 1, four of the 11 placebo patients had the "normal" gastric emptying, and by day 2, five patients fulfilled this criterion. Before administration of cisapride, four of the 12 patients fulfilled this criterion, whereas nine fulfilled the criterion after receiving cisapride. There was a large variation in gastric emptying from day 1 to day 2; a power calculation suggests that approximately 150 patients would have to be studied to determine the effect of cisapride. There was no correlation between gastric emptying and the volume of gastric aspirate or the presence of bowel sounds. Plasma cisapride concentrations 4 hrs after the third dose, during the second acetaminophen absorption test, averaged 53 ng/mL (range 20 to 111).

Rectal cisapride in the dose given achieved average plasma concentrations similar to those concentrations achieved in healthy subjects after 30 mg of cisapride rectally. There is a large variation in gastric emptying from one day to the next and large numbers of patients are required to determine if cisapride administration improves early gastric emptying in critically ill patients. The volume of gastric aspirate and the presence of bowel sounds do not correlate with gastric emptying.

Nasogastric (NG) tubes are routinely used in patients undergoing cardiac surgery. This randomized study was designed to assess gastroesophageal reflux (GER) without a NG tube (control) compared with a NG tube managed either by gravity drainage (gravity) or continuous low-grade suction (suction). Antimony pH probes were placed in the lower esophagus and trachea after induction of anesthesia in 51 patients, and pH was recorded every 5 s until the time of tracheal extubation. GER was defined as reversible decrease in esophageal pH to less than 4.0. No significant difference was found between groups in age, weight, gender, duration of postoperative ventilation, morphine use, or antiemetic use. All indicators of GER were seen more frequently in the gravity group compared with the two other groups (P < 0.001). One episode of sudden decrease in tracheal pH was observed in a patient in the gravity group, indicating tracheal aspiration, which was associated with delayed extubation and postoperative pneumonia. The absence of a NG tube is not associated with reflux, probably since the gastroesophageal sphincter remains competent. NG tubes are not routinely necessary for cardiac surgery in patients without risk factors for GER, and increase reflux risk if managed without low-grade suction.