Paul J. Matheson

Poor validity of residual volumes as a marker for risk of aspiration in critically ill patients.

Background and Aims:Elevated residual volumes (RV), considered a marker for the risk of aspiration, are used to regulate the delivery of enteral tube feeding. We designed this prospective study to validate such use. Methods:Critically ill patients undergoing mechanical ventilation in the medical, coronary, or surgical intensive care units in a university-based tertiary care hospital, placed on intragastric enteral tube feeding through nasogastric or percutaneous endoscopic gastrostomy tubes, were included in this study. Patients were fed Probalance (Nestlé USA) to provide 25 kcal/kg per day (to which 109 yellow microscopic beads and 4.5 mL of blue food coloring per 1,500 mL was added). Patients were randomized to one of two groups based on management of RV: cessation of enteral tube feeding for RV >400 mL in study patients or for RV >200 mL in controls. Acute Physiology and Chronic Health Evaluation (APACHE) III, bowel function score, and aspiration risk score were determined. Bedside evaluations were done every 4 hrs for 3 days to measure RV, to detect blue food coloring, to check patient position, and to collect secretions from the trachea and oropharynx. Aspiration/regurgitation events were defined by the detection of yellow color in tracheal/oropharyngeal samples by fluorometry. Analysis was done by analysis of variance, Spearman’s correlation, Student’s t-test, Tukey’s method, and Cochran-Armitage test. Results:Forty patients (mean age, 44.6 yrs; range, 18–88 yrs; 70% male; mean APACHE III score, 40.9 [range, 12–85]) were evaluated (21 on nasogastric, 19 on percutaneous endoscopic gastrostomy feeds) and entered into the study. Based on 1,118 samples (531 oral, 587 tracheal), the mean frequency of regurgitation per patient was 31.3% (range, 0% to 94%), with a mean RV for all regurgitation events of 35.1 mL (range, 0–700 mL). The mean frequency of aspiration per patient was 22.1% (range, 0% to 94%), with a mean RV for all aspiration events of 30.6 mL (range, 0–700 mL). The median RV for both regurgitation and aspiration events was 5 mL. Over a wide range of RV, increasing from 0 mL to >400 mL, the frequency of regurgitation and aspiration did not change appreciably. Aspiration risk and bowel function scores did not correlate with the incidence of aspiration or regurgitation. Blue food coloring was detected on only three of the 1,118 (0.27%) samples. RV was ≤50 mL on 84.1% and >400 mL on 1.4% of bedside evaluations. Sensitivities for detecting aspiration per designated RV were as follows: 400 mL = 1.5%; 300 mL = 2.3%; 200 mL = 3.0%; and 150 mL = 4.5%. Low RV did not assure the absence of events, because the frequency of aspiration was 23.0% when RV was <150 mL. Raising the designated RV for cessation of enteral tube feeding from 200 mL to 400 mL did not increase the risk, because the frequency of aspiration was no different between controls (21.6%) and study patients (22.6%). The frequency of regurgitation was significantly less for patients with percutaneous endoscopic gastrostomy tubes compared with those with nasogastric tubes (20.3% vs. 40.7%, respectively; p = .046). There was no correlation between the incidence of pneumonia and the frequency of regurgitation or aspiration. Conclusions:Blue food coloring should not be used as a clinical monitor. Converting nasogastric tubes to percutaneous endoscopic gastrostomy tubes may be a successful strategy to reduce the risk of aspiration. No appropriate designated RV level to identify aspiration could be derived as a result of poor sensitivity over a wide range of RV. Study results do not support the conventional use of RV as a marker for the risk of aspiration.

Obesity, inflammation, and the potential application of pharmaconutrition

Obesity is an emerging problem worldwide. Hospitalized obese patients often have a worse outcome than patients of normal weight, particularly in the setting of trauma and critical care. Obesity creates a low-grade systemic inflammatory response syndrome (SIRS) that is similar (but on a much smaller scale) to gram-negative sepsis. This process involves up-regulation of systemic immunity, is characterized clinically by insulin resistance and the metabolic syndrome, and puts the patient at increased risk for organ failure, infectious morbidity, and mortality. Through lipotoxicity and cytokine dysregulation, obesity may act to prime the immune system, predisposing to an exaggerated subsequent immune response when a second clinical insult occurs (such as trauma, burns, or myocardial infarction). Specialized nutrition therapy for such patients currently consists of a hypocaloric, high-protein diet. However, this approach does not address the putative pathophysiologic mechanisms of inflammation and altered metabolism associated with obesity. A number of dietary agents such as arginine, fish oil, and carnitine may correct these problems at the molecular level. Pharmaconutrition formulas may provide exciting innovations for the nutrition therapy of the obese patient.

Hypercoagulability in patients with obstructive sleep apnea

BACKGROUND Obstructive sleep apnea (OSA) has been linked to cardiovascular complications such as stroke and myocardial infarction. Previous studies demonstrate that OSA patients show elevated fibrinogen levels and increased platelet aggregation that are reversed with 1 night of nasal continuous positive airway pressure treatment (NCPAP). Questioning overall coagulability in OSA, we examined whole blood coagulability in 11 chronically NCPAP treated OSA subjects, 22 previously untreated OSA subjects, and in 16 of these after 1 night of NCPAP treatment. PATIENTS AND METHODS During full polysomnography, subjects from each group had blood drawn prior to bedtime (21:00 h) and upon waking in the morning (07:00 h). RESULTS Untreated OSA patients had faster P.M. clotting times than chronically treated OSA patients (3.33+/-0.31 versus 6.12+/- 0.66 min, P<0.05 by ANOVA). A.M. values showed similar results (4.31+/- 0.34 min versus 7.08+/-0.52 min, P<0.05 by ANOVA) for the respective groups. One overnight treatment with nasal CPAP did not produce a significant change in A.M. whole blood coagulability (4.35 +/-0.43 to 5.31+/-0.53 min; n=16; P=0.1) in 16 treated subjects. CONCLUSIONS These data indicate a relationship between obstructive sleep apnea and blood hypercoagulability status that appears to be reversed by chronic NCPAP treatment. These data suggest that NCPAP might protect against the development of cardiovascular complications in OSA patients.

Complement Activation Mediates Intestinal Injury after Resuscitation from Hemorrhagic Shock

BACKGROUND Endothelial cell injury after hemorrhage and resuscitation (HEM/RES) might contribute to intestinal hypoperfusion and mucosal ischemia. Our recent work suggests that the injury might be the result of complement activation. We hypothesized that HEM/RES causes complement-mediated endothelial cell dysfunction in the small intestine. METHODS Male Sprague-Dawley rats (195-230 g) were anesthetized and HEM to 50% of baseline mean arterial pressure for 60 minutes. Just before RES, animals received either soluble complement receptor-1 (sCR1, 15 mg/kg) to inhibit complement activation or saline vehicle. Resuscitation was with shed blood and an equal volume of saline. Two hours after RES, the small bowel was harvested to evaluate intestinal nitric oxide synthase activity (NOS), neutrophil influx, histology, and oxidant injury. RESULTS HEM/RES induced tissue injury, increased neutrophil influx, and reduced NOS activity by 50% (vs. SHAM), all of which were completely prevented by sCR1 administration. There were no observed differences in oxidant injury between the groups. CONCLUSION Histologic tissue injury, increased neutrophil influx, and impaired NOS activity after HEM/RES were all prevented by complement inhibition. Direct oxidant injury did not seem to be a major contributor to these alterations. Complement inhibition after HEM might ameliorate reperfusion injury in the small intestine by protecting the endothelial cell, reducing neutrophil influx and preserving NOS function.

Intraperitoneal Resuscitation Improves Intestinal Blood Flow Following Hemorrhagic Shock

ObjectiveTo study the effects of peritoneal resuscitation from hemorrhagic shock. Summary Background DataMethods for conventional resuscitation (CR) from hemorrhagic shock (HS) often fail to restore adequate intestinal blood flow, and intestinal ischemia has been implicated in the activation of the inflammatory response. There is clinical evidence that intestinal hypoperfusion is a major factor in progressive organ failure following HS. This study presents a novel technique of peritoneal resuscitation (PR) that improves visceral perfusion. MethodsMale Sprague-Dawley rats were bled to 50% of baseline mean arterial pressure (MAP) and resuscitated with shed blood plus 2 equal volumes of saline (CR). Groups were 1) sham, 2) HS + CR, and 3) HS + CR + PR with a hyperosmolar dextrose-based solution (Delflex 2.5%). Groups 1 and 2 had normal saline PR. In vivo videomicroscopy and Doppler velocimetry were used to assess terminal ileal microvascular blood flow. Endothelial cell function was assessed by the endothelium-dependent vasodilator acetylcholine. ResultsDespite restored heart rate and MAP to baseline values, CR animals developed a progressive intestinal vasoconstriction and tissue hypoperfusion compared to baseline flow. PR induced an immediate and sustained vasodilation compared to baseline and a marked increase in average intestinal blood flow during the entire 2-hour post-resuscitation period. Endothelial-dependent dilator function was preserved with PR. ConclusionsDespite the restoration of MAP with blood and saline infusions, progressive vasoconstriction and compromised intestinal blood flow occurs following HS/CR. Hyperosmolar PR during CR maintains intestinal blood flow and endothelial function. This is thought to be a direct effect of hyperosmolar solutions on the visceral microvessels. The addition of PR to a CR protocol prevents the splanchnic ischemia that initiates systemic inflammation.

Direct Peritoneal Resuscitation Accelerates Primary Abdominal Wall Closure after Damage Control Surgery

BACKGROUND Damage control surgery is a staged approach to the trauma patient in extremis that improves survival, but leads to open abdominal wounds that are difficult to manage. We evaluated whether directed peritoneal resuscitation (DPR) when used as a resuscitation strategy in severely injured trauma patients with hemorrhagic shock requiring damage control surgery would affect the amount of and timing of resuscitation and/or show benefits in time to abdominal closure and reduction of intra-abdominal complications. STUDY DESIGN A retrospective case-matched study of patients undergoing damage control surgery for hemorrhagic shock secondary to trauma between January 2005 and December 2008 was performed. Twenty patients undergoing standardized wound closure and adjunctive DPR were identified and matched to 40 controls by Injury Severity Score, age, gender, and mechanism of injury. A single early death was excluded because of inability to control ongoing hemorrhage. RESULTS There were no differences in age, gender, or mechanism of injury between the groups. Injury Severity Score (35.07 +/- 17.1 versus DPR 34.95 +/- 16.95; p = 0.82) and packed red blood cell administration in 24 hours (23.8 +/- 14.35 U versus DPR 26.9 +/- 14.1 U; p = 0.43) were similar between the groups. Presenting pH was similar between the study group and the DPR group (7.24 +/- 0.13 d versus DPR 7.26 +/- 0.11; p = 0.8). Time to definitive abdominal closure was significantly less in the DPR group compared with controls (DPR: 4.35 +/- 1.6 d versus 7.05 +/- 3.31; p < 0.003). DPR also allowed for a higher rate of primary fascial closure, lower intra-abdominal complication rate, and lower rate of ventral hernia formation at 6 months. Adjunctive DPR afforded a definitive wound closure advantage compared with Wittmann patch closure techniques (DPR 4.35 +/- 1.6 versus Wittmann patch 6.375 +/- 1.3; p = 0.004). CONCLUSIONS The addition of adjunctive DPR to the damage control strategy shortens the interval to definitive fascial closure without affecting overall resuscitation volumes. As a result, this mitigates intra-abdominal complications associated with open abdomen and damage control surgery and affords better patient outcomes.

Immune-enhancing enteral diet increases blood flow and proinflammatory cytokines in the rat ileum

BACKGROUND Enteral feeding improves outcome following surgery. Benefits depend on timing, route (enteral vs parenteral), and nutrient composition (standard vs immune-enhancing diets; IED). IED augments intestinal immunity and stimulates gut blood flow during absorption in a nutrient-specific manner. We hypothesize that a mechanism for the gut protective effect of IED is augmentation of blood flow to the gut-associated lymphoid tissue (GALT) in the terminal ileum. METHODS Male Sprague-Dawley rats (200-230 g) were fed for 5 days either an IED (Impact, Novartis) or an isocaloric, isonitrogenous control diet (CD, Boost, Mead-Johnson) matched to the daily caloric intake (rat chow). Rats were then anesthetized and cannulated for microsphere determination of whole organ blood flow. Blood glucose levels and blood flow to abdominal organs were determined at baseline and 30, 60, 90, and 120 min after gastric gavage (2 ml) with IED or CD. Intestinal tissues were harvested for cytokine levels (ELISA: IL-4, IL-10, IFN-gamma, and IgA). RESULTS Chronic IED increased baseline blood flow in the distal third of the small intestine compared to chow-fed and CD. Baseline blood flow was comparable between IED and CD in all other organs. CD and IED produced different blood flow patterns after gavage. CD increased blood flow compared to baseline and IED in antrum, duodenum, and jejunum. Ileal blood flow remained elevated in IED rats for 2 h, perhaps suggesting maximal blood flow. IED increased blood glucose compared to CD. Chronic IED increased IL-4 and decreased IL-10 in the terminal ileum. CONCLUSIONS Chronic IED exposure increases and sustains ileal blood flow compared to CD with altered proinflammatory cytokine expression. Our data suggest that a mechanism for the IED effect involves the selective perfusion of the terminal ileum and contiguous GALT during IED nutrient absorption.

Nitric oxide mediates redistribution of intrarenal blood flow during bacteremia

The normal or hyperdynamic circulatory response during the early phases of the systemic septic response is associated with renal microvascular constriction and can result in renal dysfunction. Intrarenal redistribution of blood flow from the outer cortex to the medulla appears to account for decreased glomerular filtration in spite of normal or elevated renal blood flow, but the mechanisms of this response are not well described. Nitric oxide is recognized as an important regulator of regional blood flow during both normal and pathologic conditions including sepsis, and we hypothesized that alterations in nitric oxide contribute to redistribution of renal blood flow during sepsis. The current study used laser Doppler fluximetry and clearance of p-aminohippuric acid (effective renal plasma flow, ERPF) to study intrarenal distribution of blood flow during basal conditions and during normodynamic Escherichia coli bacteremia, with and without inhibition of nitric oxide. Inhibition of nitric oxide in normal animals resulted in a decrease in ERPF (-19%) with a decrease in cortical flux (-39%) without alteration of medullary flux. Bacteremia resulted in a decrease in cortical flow (-17%), an increase in medullary flow (36%), and a modest reduction (-9%) in ERPF. Inhibition of nitric oxide synthase during bacteremia worsened cortical flow (-43%), reversed the increase in medullary flux (-42%), and further impaired ERPF (-28%). These data suggest that nitric oxide regulates renovascular tone during normal conditions and bacteremia, and indicate that it is a prime mediator of intrarenal redistribution of blood flow during sepsis.

Obesity-induced hepatic hypoperfusion primes for hepatic dysfunction after resuscitated hemorrhagic shock

BACKGROUND Obese patients (BMI>35) after blunt trauma are at increased risk compared to non-obese for organ dysfunction, prolonged hospital stay, infection, prolonged mechanical ventilation, and mortality. Obesity and non-alcoholic fatty liver disease (NAFLD) produce a low grade systemic inflammatory response syndrome (SIRS) with compromised hepatic blood flow, which increases with body mass index. We hypothesized that obesity further aggravates liver dysfunction by reduced hepatic perfusion following resuscitated hemorrhagic shock (HEM). METHODS Age-matched Zucker rats (Obese, 314-519 g & Lean, 211-280 g) were randomly assigned to 4 groups (n = 10-12/group): (1) Lean-Sham; (2) Lean, HEM, and resuscitation (HEM/RES); (3) Obese-Sham; and (4) Obese-HEM/RES. HEM was 40% of mean arterial pressure (MAP) for 60 min; RES was return of shed blood/5 min and 2 volumes of saline/25 min. Hepatic blood flow (HBF) using galactose clearance, liver enzymes and complete metabolic panel were measured over 4 h after completion of RES. RESULTS Obese rats had increased MAP, heart rate, and fasting blood glucose and BUN concentrations compared to lean controls, required less blood withdrawal (mL/g) to maintain 40% MAP, and RES did not restore BL MAP. Obese rats had decreased HBF at BL and during HEM/RES, which persisted 4 h post RES. ALT and BUN were increased compared to Lean-HEM/RES at 4 h post-RES. CONCLUSION These data suggest that obesity significantly contributes to trauma outcomes through compromised vascular control or through fat-induced sinusoidal compression to impair hepatic blood flow after HEM/RES resulting in a greater hepatic injury. The pro-inflammatory state of NAFLD seen in obesity appears to prime the liver for hepatic ischemia after resuscitated hemorrhagic shock, perhaps intensified by insidious and ongoing hepatic hypoperfusion established prior to the traumatic injury or shock.

Hemorrhagic shock and resuscitation-mediated tissue water distribution is normalized by adjunctive peritoneal resuscitation.

BACKGROUND Adjunctive direct peritoneal resuscitation (DPR) from hemorrhagic shock (HS) improves intestinal blood flow and abrogates postresuscitation edema. HS causes water shifts as a result of sodium redistribution and changes in transcapillary Starling forces. Conventional resuscitation (CR) with crystalloid aggravates water sequestration. We examined the compartment pattern of organ tissue water after HS and CR, and modulation of tissue edema by adjunctive DPR. STUDY DESIGN Rats were hemorrhaged (40% mean arterial pressure for 60 minutes) and assigned to four groups (n = 7): sham, no HS; HS no resuscitation; HS+CR (shed blood plus 2 volumes Ringers lactate); and HS+CR+DPR (20 mL clinical intraperitoneal (IP) dialysis fluid). Isotopic markers determined equilibrium distribution volumes [V(D)] in gut, liver, lung, and muscle by quantitative autoradiography (2-hour postresuscitation). Total tissue water (TTW) was determined by wet-dry weights. Extracellular water was measured from (14)C-mannitol V(D), and intravascular volume (IVV) from (131)I-labeled IgG V(D). Cellular and interstitial water volumes were calculated. RESULTS HS alone decreased IVV in all tissues and TTW in gut, lung, and muscle, but not liver, compared with shams. IVV remained decreased with all resuscitations despite restoration of central hemodynamics. CR caused interstitial edema in gut, liver, and muscle, and cellular edema in lung. DPR reduced (liver, muscle) or prevented (gut, lung) these volume shifts. CONCLUSIONS HS decreases IVV. HS-induced water shifts are organ-specific and prominent in gut, lung, and muscle. CR restores central hemodynamics, does not restore IVV, and alters organ-specific TTW distribution. Adjunctive DPR with IP dialysis fluid normalizes TTW and water compartment distribution and prevents edema. Combined effect of DPR and intravascular fluid replacement appears to prevent global tissue edema and improve outcomes from HS.