Impact of a monitored program of care on incidence of ventilator-associated pneumonia: results of a longterm performance-improvement project.

BACKGROUND: Ventilator-associated pneumonia (VAP) remains a major source of morbidity, mortality, and expense in the ICU despite therapies directed against it. STUDY DESIGN: A retrospective review of a prospectively developed performance-improvement project monitoring the incidence of VAP in two adjacent ICUs was conducted. In response to an excessive VAP rate, weekly multidisciplinary team meetings were instituted to review data, develop care protocols, and modify care routines. Protocol compliance was monitored daily and feedback provided weekly to the care teams. VAP rates were determined by the institutional Infection Control Committee and reviewed monthly with the ICU multidisciplinary team. Duration of the investigational period was 10 years. RESULTS: A standardized ventilator-weaning protocol was instituted with confirmed 95% use. Additional modifications of care, such as patient positioning, use of specific endotracheal tubes to minimize aspiration of supraglottic secretions, an oral-care regimen, and aggressive antibiotic stewardship were standardized, with a compliance rate >90%. VAP rates dropped from 12.8 per 1,000 patient-days in 1998 to 1.1 in 2007 in the burn trauma ICU and from 21.2 to <1 in the neurotrauma ICU in the same time frame. Also, mean ventilator length of stay decreased from 6 days to 4.2 and from 5.8 days to 4.75 simultaneously in the respective ICUs. Such performance improvement has been sustained since implementation of the program. CONCLUSION: A systematic, monitored program of standardized care protocols can markedly reduce VAP rate in the ICU.

Adrenal insufficiency in hemorrhagic shock.

Adrenal insufficiency during sepsis is well documented. The association between hemorrhagic shock and adrenal insufficiency is unclear and may be related to ischemia, necrosis, or resuscitation. This study was designed to determine the incidence of relative adrenal insufficiency in hemorrhagic shock. A retrospective review of a prospectively gathered database for patients admitted to the trauma intensive care unit with hemorrhagic shock was undertaken. A random serum cortisol of <25 mcg/dL defined relative adrenal insufficiency. All of the cortisol levels were drawn within the first 24 hours of admission. Data analyzed included demographics, length of stay, injury mechanism, infections, and mortality. Fifteen patients presented with hemorrhagic shock, with 14 of 15 meeting the criteria for relative adrenal insufficiency. The average serum cortisol level was 15.8 (9-26.8). The average APACHE II score was 18.3 (4-33), and the average Injury Severity Score was 22.5 (8-41). The mechanism was blunt trauma in 10 patients and penetrating trauma in 5. The average intensive care unit and hospital length of stay were 13.2 and 27.4 days, respectively. There were five urinary tract infections, four blood stream infections, and two wound infections. Two of the 15 patients died. Relative adrenal insufficiency appears to be common in hemorrhagic shock. Future research is warranted to elucidate the pathophysiology, as well as to prospectively determine which patients may benefit from steroid replacement.

Adrenal insufficiency in the critically III trauma population.

Acute adrenal insufficiency has been demonstrated in a number of patients with shock. This study was designed to evaluate the rate of occult adrenal insufficiency in the critically ill trauma population and to determine the impact of hypoproteinemia on the use of random cortisol levels as a marker for adrenal insufficiency. Forty-four patients were prospectively enrolled on admission to the trauma intensive care unit, with three excluded, for a total n of 41. Random total serum cortisol and albumin levels were drawn on hospital Days 1, 4, 8, and 14. Occult adrenal insufficiency was defined as a cortisol less than 25 mcg/dL in the setting of an albumin greater than 2.5 g/dL. The prevalence of cortisol less than 25 mcg/dL ranged from 51 to 81 per cent during the study period, and peaked on Days 4 and 8. Albumin 2.5 g/dL or less ranged from 37 to 60 per cent, and this prevalence also peaked on Days 4 and 8. The patients with a low albumin had a high prevalence of low cortisol, ranging from 67 to 100 per cent. The prevalence of adrenal insufficiency, with low cortisol and normal albumin, ranged from 41 to 82 per cent during the study period. None of our patients with occult adrenal insufficiency were treated with steroids, which was a decision made by the treating physicians. Among the patients with occult adrenal insufficiency, survival was 100 per cent. Occult adrenal insufficiency is common in critically ill trauma patients, and is a dynamic entity that can be acquired and even resolved during critical illness. Random cortisol of 25 mcg/dL may actually not be an adequate marker of occult adrenal insufficiency. Low albumin predicts a low cortisol. Hemodynamically stable occult adrenal insufficiency should not be treated with steroid replacement in the critically ill trauma patient, as survival in our series was 100 per cent without replacement.

Secondary abdominal compartment syndrome: risk factors and outcomes.

Secondary abdominal compartment syndrome (ACS), defined as intra-abdominal hypertension with associated pulmonary, renal, or hemodynamic compromise in the absence of preceding abdominal operation or injury, can markedly increase surgical morbidity and mortality. We performed a retrospective chart review of the physiologic parameters and outcomes of 10 patients with secondary ACS. Ten patients developed secondary ACS after aggressive resuscitation, at an average of 20.2 hours. Four of the patients sustained burns greater than 40 per cent, three of the patients had penetrating extremity trauma, one patient had blunt abdominal trauma, one patient was struck by lightning, and one patient developed a retroperitoneal bleed while on heparin. The average bladder pressure was 40.6. The average volume given in the first 24 hours was 33,001 cc (range, 12,400 to 69,000). The average base deficit at admission was -12 (range, +1 to -25). Seven of the 10 patients had decreased urine output. Nine of the 10 patients had decreased tidal volumes on pressure control ventilation. All 10 patients were hypotensive, with 7 of the 10 requiring vasopressors. Overall mortality was 60 per cent, with 43 per cent mortality for those decompressed. Prompt recognition and treatment are mandatory for survival of ACS. We recommend routine bladder pressure monitoring for patients with ongoing resuscitation greater than 500 cc/hr.

Microarray expression profiling of tissues from mice with uniparental duplications of chromosomes 7 and 11 to identify imprinted genes.

Microarray analysis allows the screening of thousands of identifiable genes in a single experiment. The challenge of this approach is to combine the new technology with established genetic tools to associate genes with specific biological function. In this study we have designed a screen to identify imprinted genes from mice with uniparental duplications of proximal Chromosomes (Chrs) 7 and 11, using microarray analysis. By comparing the expression patterns in embryonic and newborn tissues of maternally versus paternally inherited proximal Chrs 7 and 11, we have correctly identified four out of five known imprinted genes represented on a microarray. We have additionally identified two novel imprinted candidate genes as well as a differentially expressed clone that is a potential downstream target. Interpretation of the microarray data requires careful preparation of age- and strain-matched samples and attention to detail in tissue dissection technique.

The usefulness of serum troponin levels in evaluating cardiac injury.

The diagnosis and clinical significance of blunt cardiac injury remains controversial. Cardiac troponin I is not found in skeletal muscle and has a high sensitivity for myocardial ischemia or injury. We hypothesized that normal troponin levels 4 to 6 hours postinjury would effectively exclude the diagnosis of cardiac contusion. A prospective evaluation of all blunt trauma patients older than 16 and admitted with the possible diagnosis of blunt cardiac injury was undertaken. Patients in whom this diagnosis was considered had an electrocardiogram (EKG) on admission, serum troponin, CPK and isoenzymes 4 to 6 hours postinjury, and admission with overnight telemetry. Other laboratory data and radiographic imaging was obtained as indicated. Seventy-two patients met criteria for entry into the study. Data was incomplete or inaccurately obtained on six patients, and they were excluded. Forty patients had normal troponins and normal EKG's on admission and were discharged the following day without any untoward effect. Sixteen patients were admitted with abnormal EKGs. All of these 16 patients had normal troponins 4 to 6 hours after their injury. They all did well and were discharged the following day. Ten patients had elevated troponins 4 to 6 hours after injury. One died two days later from refractory cardiogenic shock. Another was noted to have severely depressed left ventricular function by echocardiography. The other eight patients sustained no cardiac sequelae and were discharged once recovered from injuries. In the hemodynamically stable patient a normal troponin 4 to 6 hours after injury excludes clinically significant blunt cardiac injury. This holds true whether the admission EKG is normal or not. An elevated troponin does not definitively diagnose a clinically significant contusion. However, these patients should be monitored at least for 24 hours. Patients suspicious for cardiac contusions who have normal troponins and no other serious injuries may be safely discharged to go home from the emergency department.

Modulation of microvascular permeability by 21-aminosteroids after burn injuries.

Burn injuries initiate lipid peroxidation in capillary endothelial cells and cause alterations in microvascular permeability, with subsequent leakage of fluid and protein from the plasma into the interstitium. We evaluated the effects of two lazaroid compounds (U74389F and U75412E) on alterations in microvascular permeability that resulted from burn injuries. A canine model was used for the evaluation of microvascular permeability at the site of the burn injury with the use of a measure of the reflection coefficient (sigma(d)). Hindpaw lymph flow, lymph and plasma total protein concentrations, and arterial, venous, and capillary pressures were measured before burn injuries and for 6 hours in 6 different groups. Footpaw weight gain was then calculated as the percentage of increase of experimental hindpaw relative to the contralateral paw. The damage was attenuated by 20 mg/kg of lazaroid U75412E given before the injuries, but a lower dose was not effective. This agent was also effective in limiting edema formation, as evidenced by changes in footpaw weight gain. However, the administration of either lazaroid compound produced no significant effect on the burn-induced changes in capillary permeability. We conclude that these lazaroids do not prevent burn-induced changes in permeability at the site of injury when administered after an injury. U75412E administered before the injury was effective in limiting the alterations in microvascular permeability.

Regional blood flow response to hypothermia in premature, newborn, and neonatal piglets.

BACKGROUND/PURPOSE: Hypothermia (HT) remains a significant stress to the newborn and has been implicated in the pathogenesis of necrotizing enterocolitis (NEC). The authors assessed the effect of transient HT (32 degrees C) on regional organ blood flow in anesthetized piglets at age 7 to 10 days preterm (PREM), 1 to 2 days (NB), and 1 to 2 weeks (NEO). METHODS: Radiolabeled microspheres were used to determine organ blood flows (mL/min/g) at baseline, 15, and 60 minutes after HT and 60 minutes after rewarming to baseline core temperature. RESULTS: Heart rate and cardiac output decreased significantly in all groups. Cardiac flow decreased significantly in the NEO group, and central nervous system (CNS) flow decreased significantly in the NB and NEO groups. Both returned to baseline levels after rewarming. The PREM group experienced decreased cardiac, CNS, and intestinal blood flows but not to significant levels. NB and NEO intestinal blood flow showed significant decreases, which remained so after rewarming (a response not seen in hypoxia or hypovolemia). Cardiac output did not return to baseline levels in any group. CONCLUSIONS: HT causes derangements in organ blood flows that differ from other deleterious stimuli such as hypoxia and hypovolemia. The prolonged intestinal ischemia supports HT as a factor in the development of NEC. This delay may offer opportunity to intervene in an attempt to lessen ischemia-reperfusion injury.

Organ blood flow redistribution in response to hypoxemia in neonatal piglets.

This study was designed to determine the effects of severe hypoxemia on newborn piglet visceral blood flow. While the hemodynamic effects of a severe hypoxemic insult are well characterized in newborn animals, its impact on organ perfusion in premature infants is not well characterized. Cannulas were placed in the femoral vessels and left atrium of term (1-14 days old) and prematurely delivered (cesarean section at 90% of term gestation) piglets. After stabilization, some animals were subjected to 1 h of ventilator-controlled hypoxia (yielding PaO2 approximately = 30-40 torr) followed by 30 min of reoxygenation; the remaining animals served as unchallenged controls. Radiolabeled microspheres were injected in all animals at times 0 min (baseline), 5 and 60 min (hypoxia), and 90 min (reoxygenation). Blood flows (mL/min/g tissue) to organs were determined using reference organ techniques. Control animals displayed no alterations in any of the variables monitored. Throughout the experimental period, organ blood flows were almost uniformly lower (p<.05, ANOVA) in premature versus term animals. The trend toward increased cerebral and cardiac blood flows during hypoxia observed in the premature piglets was similar to that of term animals, but of lower magnitude. In term piglets, hypoxia produced an immediate and significant (*p<.05) decline in small-intestinal blood flow followed by autoregulatory escape (2.02+/-0.17 mL/min/g at time 0, 1.56+/-0.15 mL/min/g at 5 min hypoxia, 1.88+/-0.18 mL/min/g at 60 min hypoxia, 2.26+/-0.19 mL/min/g at 30 min reoxygenation), an effect not readily observed in the premature piglets (0.48+/-0.10 mL/min/g at time 0, 0.44+/-0.07 mL/min/g at 5 min hypoxia, 0.46+/-0.10 mL/min/g at 60 min hypoxia, 0.42+/-0.08 mL/min/g at 30 min reoxygenation). However, mucosal blood flows measured in these younger animals declined throughout the experimental period to almost 50% of baseline, compared to a complete restoration to baseline blood flow observed following reoxygenation of term piglets. Intestinal blood flow in premature infants is small when compared to term animals, and alterations in small intestinal blood mucosal flow induced by hypoxia appear less well tolerated by the premature animals. Taken together, this may in part account for the increased risk of developing intestinal ischemic diseases in premature infants who are even temporarily exposed to a severe hypoxic challenge.

Laparoscopic versus open appendectomy.

This prospective clinical study was done because our initial retrospective review suggested that laparoscopic appendectomy (LA) offers no significant advantages over open appendectomy (OA) yet is significantly more expensive. From July 1992 to August 1993, 57 patients were approached preoperatively for randomization to either LA (n = 19) or OA (n = 18). There were no statistically significant differences between the LA and OA groups in operative risk: mean age, 28 +/- 2 vs 26 +/- 2 years; percent female, 26% vs 22%; body mass index, 24 +/- 0.8 vs 26 +/- 1.2 kg/m2. All patients were either ASA class I or class II, 78% in each group being class II. The differences between the LA and OA groups in mean operating time required (93 +/- 12 vs 87 +/- 8 minutes), postoperative intramuscular narcotic analgesic usage (24 +/- 6 vs 26 +/- 6 hours), postoperative hospital stay (57 +/- 12 vs 66 +/- 10 hours), and return to normal activity (20 +/- 6 vs 14 +/- 3 days) were also not significant. However, LA was much more expensive because of higher operating room charges. The mean total hospital bill was $4,600 +/- $160 for the LA group and $1,700 +/- $70 for the OA group. This prospective study corroborated our previous analysis. Laparoscopic appendectomy is safe, effective, and expensive and overall has no greatly significant advantages over open appendectomy.

Reduction of Aedes dorsalis by enhancing tidal action in a northern California marsh.

Full tidal action was restored to a 28-ha marshland in the brackish region of the San Francisco Bay Estuary to evaluate the impact of increased tidal circulation on Aedes dorsalis abundance. One year after project completion, mosquito abundance had decreased by 98.7%, from an average of 3.6 to 0.3 4th-instar larvae per dip. Larvicide applications have consequently been reduced from approximately 6 to zero per year. The effects on the marsh plant community and marsh elevation were assessed during the first 2.3 years since project completion. Total coverage by sedges, rushes, reeds, cattails, and brass buttons increased almost 80% at the expense of pickleweed (-65%) and peppergrass (-34%). Sedimentation on the marsh plain has averaged 1.2 cm/year, which is about 10 times greater than the average rate of sea level rise for the region. In general, the marsh ecosystem has begun to acquire characteristics that typify immature, highly productive, fully tidal brackish marshes of the region.

Effects of graded thermal injury on microvascular permeability at the site of injury.

To define whether capillary permeability traits at the site of a burn differ according to injury severity, a canine hind leg lymphatic was cannulated to measure macromolecular permeability in response to three different scalding solutions. Leg venous pressure was raised to approximately 40 mm Hg and maintained until a minimal lymph-to-plasma total protein ratio (CL/CP)min and steady-state lymph flow (QL; microliter/min/100 g) was attained. The protein reflection coefficient (1-CL/CP), fluid filtration coefficient (Kf; microliter/min/mm Hg/100 g), and QL were determined before and for 6 hr after a 5-sec hind paw immersion in either 100 degrees C (n = 7), 80 degrees C (n = 7), or 70 degrees C (n = 7) water. A group of five animals served as controls. In the absence of any systemic hemodynamic alterations, the 100 and 80 degrees C scald groups experienced significant (P < 0.05, ANOVA) increases in QL, CL/CP, and Kf as compared to respective preburn values and time-matched unburned control values. Most monitored parameters were significantly higher following 100 degrees C injury vs 80 degrees C injury. Parameters in the 70 degrees C group did change after scald, but were not significantly different from preburn values or from the control group. Alterations in capillary permeability to protein and fluid flux measured at the burn site are graded, not all or none phenomena, being dependent upon the severity of injury.

Effects of pentafraction administration on microvascular permeability alterations induced by graded thermal injury.

BACKGROUND: Pentafraction is a pentastarch derivative hypothesized to limit burn edema by "sealing" damaged capillaries, restoring a barrier to fluid translocation and macromolecular (protein) flux. METHODS: Canine hind paw lymph flow (QL) and lymph (CL) and plasma (CP) protein concentrations were measured before and for 6 hours after (1) 5-second 100 degrees C (n = 6) or 80 degrees C (n = 6) foot paw scald, (2) 100 degrees C (n = 5) or 80 degrees C (n = 5) foot paw scald followed 30 minutes later by a 4 cc/kg bolus of 6% pentafraction, or (3) pentafraction infusion without scald (n = 5). Before scald or pentafraction infusion, hind paw venous pressure was elevated and maintained by outflow restriction until a steady state, minimal CL/CP was reached. The reflection coefficient, sigma d, was determined as 1-CL/CP, and the (fluid) filtration coefficient (Kf) was calculated. RESULTS: Scalding uniformly produced statistical (p < 0.05, ANOVA) increases in QL, CL/CP, sigma d, Kf, and paw weight gain. Postburn pentafraction infusion produced no enduring alterations in any measured parameter as compared with those of animals who received a matched severity scald without pentafraction. CONCLUSIONS: Pentafraction does not appreciably ameliorate the adverse microcirculatory consequences observed at the site of burn injury.

The effects of albumin administration on microvascular permeability at the site of burn injury.

In a canine hind leg model, lymph flow (QL), lymph (CL), and plasma (CP) total protein concentrations, the reflection coefficient for total proteins (sigma d), and the filtration coefficient (Kf) were determined before and for 6 hours after a 5-second 100 degrees C hind paw scald (3% total body surface area, TBSA). Before injury, hind leg venous pressure was elevated and maintained by outflow restriction until a minimal, steady-state CL/CP ratio was achieved. Albumin (5%) was infused 30 minutes after the scald at low (0.4 mL/kg/% TBSA) or high (2 mL/kg/% TBSA) doses. Scald uniformly increased QL, CL/CP, Kf, and paw weight gain (PWG). Whereas postburn infusion of low-dose albumin mildly attenuated increases in CL/CP and PWG noted in scald-alone animals, no differences were noted between the scald and scald/high-dose albumin groups.

Tumor necrosis factor-induced mortality is reversed with cyclooxygenase inhibition.

OBJECTIVE: The authors hypothesized that TNF would induce eicosanoid synthesis, and a cyclooxygenase inhibitor would attenuate both eicosanoid synthesis and improve survival in an LD90 TNF-induced (150 ng/kg/i.v./5 min) mortality model. SUMMARY BACKGROUND DATA: Tumor necrosis factor is a cardinal mediator in sepsis; however, little is known about its effects on arachidonate metabolism. METHODS: Conscious male rats with carotid arterial and jugular venous catheters were randomized for mortality: group I, TNF alone (150 kg/i.v./15 min, n = 30); group II, ibuprofen (30 mg/kg/i.v. at t = -20 and +240 min), plus TNF, (n = 28); and for hemodynamics, eicosanoid synthesis, blood gases: group III, TNF alone, (n = 8); group IV, ibuprofen + TNF (n = 8); group V, monoclonal antibody to TNF plus TNF (n = 8). Mortality was determined at 4-72 hr. Other parameters determined over 4 hours (0, 5, 60, 120, 240 min). RESULTS: TNF stimulated synthesis of (a) TXB2 (71 +/- 30 pg/ml, mean +/- SE at base vs. 117 +/- 18 at 4 hr, p < 0.02); (b) PGE2 (70 +/- 6 pg/ml at base vs. 231 +/- 68 at 4 hr, p < 0.02); (c) 6PGF (52 +/- 6 pg/ml at base vs. 250 +/- 80 at 4 hr, p < 0.02). Ibuprofen significantly (p < 0.05) inhibited eicosanoid synthesis from TNF. TNF-induced mortality (87%, 26/30) was dramatically decreased with ibuprofen (11%, 3/28), at 4, 24, and 72 hr (p < 0.01). Monoclonal antibody to TNF prevented all abnormalities and had 100% survival. Hemodynamic events were similar in both groups, but metabolic acidosis was attenuated with ibuprofen. CONCLUSIONS: TNF stimulates arachidonic acid metabolism in vivo. A cyclooxygenase inhibitor attenuates eicosanoid synthesis and dramatically improves survival. TNF appears to have different effect on tissues that synthesize certain eicosanoids. Hypotension from TNF is not mediated via the eicosanoids. TNF-induced mortality, like endotoxemia/sepsis may be mediated, in part, via arachidonic acid metabolites. These new findings support the notion that cyclooxygenase inhibitors may be used as adjunctive therapy in clinical sepsis.