Lee C. Woodson

Regional Perfusion Abnormalities With Phenylephrine During Normothermic Bypass

BACKGROUND Hypotension and vasopressors during cardiopulmonary bypass may contribute to splanchnic ischemia. The effect of restoring aortic pressure on visceral organ, brain, and femoral muscle perfusion during cardiopulmonary bypass by increasing pump flow or infusing phenylephrine was examined. METHODS Twelve anesthetized swine were stabilized on normothermic cardiopulmonary bypass. After baseline measurements, including regional blood flow (radioactive microspheres), aortic pressure was reduced to 40 mm Hg by decreasing the pump flow. Next, aortic pressure was restored to 65 mm Hg either by increasing the pump flow or by titrating phenylephrine. The animals had both interventions in random order. RESULTS At 40 mm Hg aortic pressure, perfusion to all visceral organs and femoral muscle, but not to the brain, was significantly reduced. Increasing pump flow improved perfusion to the pancreas, colon, and kidneys. In contrast, infusing phenylephrine (2.4 +/- 0.6 micrograms.kg-1.min-1) increased aortic pressure but failed to improve splanchnic perfusion, so that significant perfusion differences existed between the pump flow and phenylephrine intervals. CONCLUSIONS Increasing systemic pressure during cardiopulmonary bypass with phenylephrine causes significantly lower values of splanchnic blood flow than does increasing the pump flow. Administering vasoconstrictors during normothermic cardiopulmonary bypass may mask substantial hypoperfusion of splanchnic organs despite restoration of perfusion pressure.

Endotoxin (LPS) increases mesenteric vascular resistance (MVR) and bacterial translocation (BT).

Endotoxemia is responsible for many of the pathophysiologic alterations that occur with Gram-negative sepsis. We utilized a chronic ovine model to determine the hemodynamic disturbances in the gastrointestinal tract during endotoxemia. Sheep with indwelling arterial, venous, and pulmonary arterial catheters were used. An ultrasonic flow probe was placed on the cephalic mesenteric artery. The animals were subjected to: 1) Ringers lactate infusion (sham n = 6); or 2) 1.5 mcg/kg E. coli endotoxin (n = 6) over over a period of one half hour and were monitored for 48 hours. They were then sacrificed and specimens of mesenteric lymph node, liver, spleen, kidney, and lung obtained for bacteriologic cultures and histologic analysis. Sheep receiving endotoxin showed more than 50% reduction in the mesenteric blood flow. Mesenteric vascular resistance increased while non-mesenteric systemic vascular resistance decreased. The increase in the total systemic vascular resistance, noted during endotoxemia, was thus likely due to the increase in the mesenteric vascular resistance. At autopsy there were positive cultures for microorganism in the mesenteric lymph nodes in six out of six sheep with endotoxemia as compared to one out of six of control. Thus the vasoconstriction in the mesenteric areas may have resulted in bacterial translocation from the GI tract.

Intranasal dexmedetomidine premedication is comparable with midazolam in burn children undergoing reconstructive surgery.

Preoperative anxiety and emergence delirium in children continue to be common even with midazolam premedication. Midazolam is unpleasant tasting even with a flavored vehicle and as a result, patient acceptance is sometimes poor. As an alternative, we evaluated dexmedetomidine administered intranasally. Dexmedetomidine an alpha-2 adrenergic agonist is tasteless, odorless, and painless when administered by this route. Alpha-2 adrenergic agonists produce sedation, facilitate parental separation, and improve conditions for induction of general anesthesia, while preserving airway reflexes. Institutional review board approval was obtained to study 100 pediatric patients randomized to intranasal dexmedetomidine (2 μg/kg) or oral midazolam (0.5 mg/kg) administered 30 to 45 minutes before the surgery. Subjects received general anesthesia with oxygen, nitrous oxide, isoflurane, and analgesics (0.05–0.1 mg/kg morphine or 0.1 mg/kg methadone). Nurses and anesthetists were blinded to the drug administered and evaluated patients for preoperative sedation, conditions for induction of general anesthesia, emergence from anesthesia, and postoperative pain. Responses of 100 patients (50 dexmedetomidine and 50 midazolam) were analyzed. Dexmedetomidine (P = .003) was more effective than midazolam at inducing sleep preoperatively. Dexmedetomidine and midazolam were comparable for conditions at induction (P > 0.05), emergence from anesthesia (P > 0.05), or postoperative pain (P > 0.05). Both drugs were equieffective in these regards. In pediatric patients, dexmedetomidine 2 μg/kg administered intranasally and midazolam 0.5 mg/kg administered orally produced similar conditions during induction and emergence of anesthesia. Intranasal administration of dexmedetomidine is more effective at inducing sleep and in some circumstances offers a useful alternative to oral midazolam in children.

Diagnosis and grading of inhalation injury.

Patients with respiratory injury resulting from inhalation of smoke or other chemical irritants experience high rates of morbidity and mortality. Even isolated inhalation injury can carry a significant risk of mortality or permanent pulmonary dysfunction. When combined with cutaneous burns, inhalation injury increases fluid requirements for resuscitation, the incidence of pulmonary complications, and the mortality rate. The diagnosis of inhalation injury is generally recognized as an important but inconsistent indicator of increased morbidity and mortality in burn patients. Remarkable progress has been achieved in the treatment of cutaneous burns. In recent decades, there has been a dramatic decline in the mortality from large burns. In contrast, despite considerable advances in our knowledge of the pathophysiology of inhalation injury, there are few specific therapeutic options and patient care is largely supportive. Although several studies have suggested a decrease in the mortality associated with inhalation injury, these changes would result from overall improvements in care and not so much from interventions aimed specifically at inhalation injury. There is general agreement that advances in the treatment of inhalation injury have not kept pace with improvements in the care of cutaneous burns. In our own institution the mortality rates for patients with inhalation injury have not changed in the past 20 years. Several factors explain the slower progress of improvements in the treatment of inhalation injuries. Inhalation injuries present an inherently more complex clinical problem. Whereas burned cutaneous tissue can be excised and replaced with viable grafted tissue, injured tissues of the lung must be protected from further injury while host mechanisms repair damage. In addition, many of the sequelae of inhalation injury result from an inflammatory response involving a large number of mediators that remain incompletely understood, despite remarkable progress in this area. In critically ill burn patients there are multiple mechanisms besides inhalation injury that may contribute to acute lung injury (eg, sepsis, ventilator induced injury, or systemic inflammatory response to the burns). As a result, although inhalation injury has a profound effect on the burn patient’s hospital course it can be difficult separate the contribution of the effects of smoke inhalation from these other mechanisms. Several features of our approach to the study of inhalation injury have also impaired progress. One major hurdle for clinicians studying inhalation injury has been the lack of uniformity in the criteria for diagnosis of inhalation injury and the absence of a generally accepted and applied system for quantifying the intensity of the injury. Without uniformity of diagnostic criteria, outcome data from different institutions are very difficult or impossible to compare. If one group includes only patients who require intubation and mechanical ventilation in their studies while another includes all patients with an abnormal Xe lung scan, clinical outcomes from the two studies are difficult to compare. In addition, most centers do not treat enough inhalation injuries to provide sufficient statistical power. Multicenter studies could overcome this deficiency by allowing several centers to pool their experience. However, until conventions for the description of clinical status are agreed upon, credible multicenter studies are not possible. The need for standardized diagnostic criteria and a system for quantifying inhalation injury is recognized as a major priority and has been documented in the burn literature for several decades. Reasons why these obstacles persist will have to be identified and addressed before conventions can be reached.

Increasing organ blood flow during cardiopulmonary bypass in pigs : comparison of dopamine and perfusion pressure

OBJECTIVE To determine whether low-dose dopamine infusion (5 micrograms/kg/min) during cardiopulmonary bypass selectively increases perfusion to the kidney, splanchnic organs, and brain at low (45 mm Hg) as well as high (90 mm Hg) perfusion pressures. DESIGN Randomized crossover trial. SETTING Animal research laboratory in a university medical center. SUBJECTS Ten female Yorkshire pigs (weight 29.9 +/- 1.2 kg). INTERVENTION Anesthetized pigs were placed on normothermic cardiopulmonary bypass at a 100-mL/kg/min flow rate. After baseline measurements, the animal was subjected, in random sequence, to 15-min periods of low perfusion pressure (45 mm Hg), low perfusion pressure with dopamine (5 micrograms/kg/min), high perfusion pressure (90 mm Hg), and high perfusion pressure with dopamine. Regional perfusion (radioactive microspheres) was measured in tissue samples (2 to 10 g) from the renal cortex (outer two-third and inner one-third segments), stomach, duodenum, jejunum, ileum, colon, pancreas, and cerebral hemispheres. MEASUREMENTS AND MAIN RESULTS Systemic perfusion pressure was altered by adjusting pump flow rate (r2 = .61; p < .05). In the kidney, cortical perfusion pressure increased from 178 +/- 16 mL/min/100 g at the low perfusion pressure to 399 +/- 23 mL/min/100 g at the high perfusion pressure (p < .05). Perfusion pressure augmentation increased the ratio of outer/inner renal cortical blood flow from 0.9 +/- 0.1 to 1.2 +/- 0.1 (p < .05). At each perfusion pressure, low-dose dopamine had no beneficial effect on renal perfusion or flow distribution. Similar results were found in the splanchnic organs, where regional perfusion was altered by perfusion pressure but not by dopamine. In contrast, neither changing perfusion pressure nor adding low-dose dopamine altered blood flow to the cerebral cortex. CONCLUSIONS These data indicate that the lower autoregulatory limits of perfusion to the kidneys and splanchnic organs differ from those limits to the brain during normothermic bypass. Selective vasodilation from low-dose dopamine was not found in renal, splanchnic, or cerebral vascular beds. Increasing the perfusion pressure by pump flow, rather than by the addition of low-dose dopamine, enhanced renal and splanchnic but not cerebral blood flows during cardiopulmonary bypass.

Acute and perioperative care of the burn-injured patient.

Care of burn-injured patients requires knowledge of the pathophysiologic changes affecting virtually all organs from the onset of injury until wounds are healed. Massive airway and/or lung edema can occur rapidly and unpredictably after burn and/or inhalation injury. Hemodynamics in the early phase of severe burn injury is characterized by a reduction in cardiac output and increased systemic and pulmonary vascular resistance. Approximately 2 to 5 days after major burn injury, a hyperdynamic and hypermetabolic state develops. Electrical burns result in morbidity much higher than expected based on burn size alone. Formulae for fluid resuscitation should serve only as guideline; fluids should be titrated to physiologic endpoints. Burn injury is associated basal and procedural pain requiring higher than normal opioid and sedative doses. Operating room concerns for the burn-injured patient include airway abnormalities, impaired lung function, vascular access, deceptively large and rapid blood loss, hypothermia, and altered pharmacology.

Management of pain and other discomforts in burned patients

Abstract Although a multidisciplinary approach including nonpharmacological modes of management are essential, pharmacological treatment remains the cornerstone of pain control in patients with burn injuries. Drug and dose selection must be made in the context of systemic changes that evolve over time and alter pharmacokinetics and pharmacodynamics. Opioids are the mainstay of therapy but are associated with certain adverse effects such as opiate induced hyperalgesia. A newly appreciated problem. neuropathic pain, is characterized by burning and itching in the areas of newly regenerating skin and at amputation site. Effective pharmacological analgesia requires the concomitant treatment of anxiety, depression and PTSD with anxiolytics and antidepressants to control the pain syndrome following burn injury. Pain protocols facilitate the systematic pain management. New non pharmacologic approaches such as virtual reality now have demonstrated effectiveness. Burn pain comprises background, breakthrough, procedural and postoperative pain. Each type of pain requires different drugs, doses, or strategies.

Percutaneous venovenous perfusion-induced systemic hyperthermia for advanced non-small cell lung cancer: initial clinical experience.

BACKGROUND Venovenous perfusion-induced systemic hyperthermia raises core body temperature by extracorporeal heating of the blood. Five patients with advanced non-small cell lung carcinoma stage IV (4.4+/-1 months after initial diagnosis) received venovenous perfusion-induced systemic hyperthermia to 42.5 degrees C (core temperature) to assess technical and patient risks. METHODS After general anesthesia and systemic heparinization (activated clotting time > 300 seconds), percutaneous cannulation of the right internal jugular vein (15F) for drainage and common femoral vein (15F) for reinfusion allowed extracorporeal flow rates up to 1,500 mL/min (20 mL x kg(-1) x min(-1)) with the ThermoChem System. This device uses charcoal-based sorbent for electrolyte homeostasis. Six monitored sites (rectal, bladder, tympanic x2, nasopharyngeal, and esophageal) determined average core temperature. RESULTS All patients achieved a core target temperature of 42.5 degrees C for 2 hours. Electrolyte balance was maintained throughout hyperthermia (mean) in mmol/L: Na+, 136.2+/-2.2 mmol/L; K+, 4.0+/-0.3 mmol/L; Ca2+, 4.1+/-0.2 mg/dL; Mg2+, 1.9+/-0.1 mg/dL; PO4-, 4.5+/-0.9 mg/dL). Plasma cytokine concentration revealed significant heat-induced activation of proinflammatory and antiinflammatory cascades. All patients exhibited systemic vasodilation requiring norepinephrine infusion, 4 of 5 patients required vigorous diuresis, and 3 of 5 required intubation for 24 to 36 hours because of pulmonary edema or somnolence, with full recovery. Average length of hospital stay was 5.4 days. Serial tumor measurements (1 patient withdrew) revealed a decrease (64.5%+/-18%) in tumor size in 2 patients, no change in 1, and enlargement in 1, with no 30-day mortality. Median survival after hyperthermia treatment was 172 days (range, 40 to 271 days). CONCLUSIONS Venovenous perfusion-induced systemic hyperthermia is feasible and provides the following potential advantages for better tumoricidal effect: (1) homogeneous heating, and (2) a higher sustained temperature.

Splanchnic oxygen consumption is impaired during severe acute normovolemic anemia in anesthetized humans

Background:In conscious humans, reduction in hemoglobin concentration to 5 g/dl did not produce inadequate systemic oxygenation. However, systemic measures of inadequate oxygenation may not be sufficiently sensitive to detect inadequate oxygenation in individual organs such as splanchnic organs. The authors tested the hypothesis that acute normovolemic anemia to hemoglobin less than 6.0 g/dl in anesthetized humans reduces splanchnic oxygen consumption because of diminished whole body oxygen delivery. Methods:Elective spine (n = 12) and abdominal (n = 7) surgery patients underwent acute normovolemic anemia to decrease the hemoglobin concentration close to 6.0 g/dl. The authors assessed the development of supply-dependent conditions in systemic and regional vascular beds by two primary measures before and after acute normovolemic anemia: oxygen consumption and surrogate biochemical markers of anaerobic metabolism, including plasma lactate, regional lactate kinetics, and ketone body ratio. Results:When hemoglobin was reduced from 13.6 ± 1.2 to 5.9 ± 0.3 g/dl, oxygen supply dependency occurred in the splanchnic and preportal tissues but not at the systemic level. Regional supply dependency was accompanied by biochemical markers of anaerobic metabolism. Conclusions:In anesthetized humans, a reduction in hemoglobin to 5.9 g/dl by acute normovolemic anemia diminished splanchnic and preportal whole body oxygen delivery and impaired splanchnic and preportal oxygen consumption. This was accompanied by increased plasma levels of regional lactate and an increased &bgr;-hydroxybutyrate–to–acetoacetate ratio. These findings suggest that the risk to the gastrointestinal tract during acute normovolemic anemia may be underestimated.

Giving new life to old lungs: methods to produce and assess whole human paediatric bioengineered lungs.

We report, for the first time, the development of an organ culture system and protocols to support recellularization of whole acellular (AC) human paediatric lung scaffolds. The protocol for paediatric lung recellularization was developed using human transformed or immortalized cell lines and single human AC lung scaffolds. Using these surrogate cell populations, we identified cell number requirements, cell type and order of cell installations, flow rates and bioreactor management methods necessary for bioengineering whole lungs. Following the development of appropriate cell installation protocols, paediatric AC scaffolds were recellularized using primary lung alveolar epithelial cells (AECs), vascular cells and tracheal/bronchial cells isolated from discarded human adult lungs. Bioengineered paediatric lungs were shown to contain well‐developed vascular, respiratory epithelial and lung tissue, with evidence of alveolar–capillary junction formation. Types I and II AECs were found thoughout the paediatric lungs. Furthermore, surfactant protein‐C and ‐D and collagen I were produced in the bioengineered lungs, which resulted in normal lung compliance measurements. Although this is a first step in the process of developing tissues for transplantation, this study demonstrates the feasibility of producing bioengineered lungs for clinical use. Copyright