PubMed Health⌕ Search

Biomedical subjects

Kenneth G Proctor

Publications and source records attributed to Kenneth G Proctor.

27 records · Page 2Linked to original sources
PubMed2003

Cerebral perfusion pressure directed therapy following traumatic brain injury and hypotension in swine.

There is a paucity of studies, clinical and experimental, attesting to the benefit of cerebral perfusion pressure (CPP) directed pressor therapy following traumatic brain injury (TBI). The current study evaluates this therapy in a swine model of TBI and hypotension. Forty-five anesthetized and ventilated swine received TBI followed by a 45% blood volume bleed. After 1 h, all animals were resuscitated with 0.9% sodium chloride equal to three times the shed blood volume. The experimental group (PHE) received phenylephrine to maintain CPP > 80 mm Hg; the control group (SAL) did not. Outcomes in the first phase (n = 33) of the study were as follows: cerebro-venous oxygen saturation (S(cv)O(2)), cerebro-vascular carbon dioxide reactivity (DeltaS(cv)O(2)), and brain structural damage (beta-amyloid precursor protein [betaAPP] immunoreactivity). In the second phase (n = 12) of the study, extravascular blood free water (EVBFW) was measured in the brain and lung. After resuscitation, intracranial and mean arterial pressures were >15 and >80 mm Hg, respectively, in both groups. CPP declined to 64 +/- 5 mm Hg in the SAL group, despite fluid supplements. CPP was maintained at >80 mm Hg with pressors in the PHE group. PHE animals maintained better S(cv)O(2) (p < 0.05 at 180, 210, 240, 270, and 300 min post-TBI). At baseline, 5% CO(2) evoked a 16 +/- 4% increase in S(cv)O(2), indicating cerebral vasodilatation and luxury perfusion. By 240 min, this response was absent in SAL animals and preserved in PHE animals (p < 0.05). Brain EVBFW was higher in SAL animals; however, lung EVBFW was higher in PHE animals. There was no difference in betaAPP immunoreactivity between the SAL and PHE groups (p > 0.05). In this swine model of TBI and hypotension, CPP directed pressor therapy improved brain oxygenation and maintained cerebro-vascular CO(2) reactivity. Brain edema was lower, but lung edema was greater, suggesting a higher propensity for pulmonary complications.

Animals↗
PubMed2003

Splanchnic perfusion during delayed, hypotensive, or aggressive fluid resuscitation from uncontrolled hemorrhage.

The purpose of this study was to determine the effect of three different fluid resuscitation strategies on splanchnic perfusion in a clinically relevant model of uncontrolled hemorrhage after liver trauma. Anesthetized swine were instrumented with a gastric near-infrared spectroscopy probe (GStO2), a jejunal tonometer (PrCO2), a portal vein catheter (SpvO2, lactate), and an ultrasonic blood flow probe on the superior mesenteric artery. The liver was lacerated to produce uncontrolled hemorrhage and a shock state characterized by a 40-60% decrease in cardiac output and a decrease in mean arterial pressure (MAP) to 42 +/- 1 mmHg. Animals were randomly assigned to either delayed resuscitation (n = 6); hypotensive resuscitation with lactated Ringer's infusion to MAP = 60 mmHg (n = 6); or aggressive resuscitation with LR to MAP >/= 75 mmHg (n = 6). For the remainder of the protocol, the treatment was identical. The data showed that blood loss (47 +/- 7 and 45 +/- 10 mL/kg) and total fluid requirements (118 +/- 73 and 171 +/- 85 mL/kg) were similar with either hypotensive or aggressive resuscitation. In contrast, with delayed resuscitation, both values were lower (27 +/- 2 mL/kg and 87 +/- 33 mL/kg, both P < 0.05). Despite aggressive resuscitation, SpvO2 and GstO2 were about 10% lower (both P < 0.05 within group) and PrCO2 was about 20 mmHg higher (P < 0.05 within group) than the corresponding values in the other two groups. Thus, delayed resuscitation minimized the blood loss but did not restore tissue oxygenation, whereas aggressive resuscitation was associated with maximal blood loss and splanchnic hypoperfusion. For this reason, it is reasonable to conclude that hypotensive resuscitation might be an effective strategy to maintain splanchnic perfusion after blunt abdominal trauma and uncontrolled hemorrhage.

Acid-Base Equilibrium↗
PubMed2003

Novel resuscitation strategy for pulmonary contusion after severe chest trauma.

BACKGROUND: Adenosine A2a receptor stimulation can increase coronary perfusion and also reduce leukocyte-mediated inflammatory responses in some conditions. Hextend is a novel colloid solution that may have antioxidant properties. All these actions might be beneficial after severe chest trauma, but have never been investigated. To fill these gaps, this study evaluated the therapeutic potential of a novel adenosine A2a agonist during fluid resuscitation from severe chest trauma with either standard-of-care crystalloid or Hextend. METHODS: Anesthetized, ventilated swine received unilateral, blunt trauma to the right chest via captive bolt gun, followed by a 10- to 12-mL/kg arterial hemorrhage. After 25 minutes of shock, ATL-146e was started (10 ng/kg/min intravenously for 180 minutes). After an additional 5 minutes, the minimum amount of either colloid (Hextend, 5% hetastarch in lactate-buffered, balanced electrolyte solution) or crystalloid (lactated Ringer's [LR] solution) was administered to maintain mean arterial pressure > 70 mm Hg and heart rate < 100 beats/min and to correct lactate for 180 minutes postinjury. Cardiopulmonary function was monitored and serial bronchoalveolar lavage samples were analyzed for protein, leukocyte infiltration, and expression of cyclooxygenase (COX)-1 and COX-2 isozymes as markers of the inflammatory cascade. RESULTS: Fluid requirements were reduced by half with Hextend compared with LR (p < 0.05). ATL-146e in either Hextend or LR transiently increased cardiac output, cardiac contractility, and systemic oxygen delivery (all p < 0.05). Pao(2)/Fio(2) ratio was 50 to 100 higher and bronchoalveolar lavage leukocytes were reduced by half with Hextend versus LR (both p < 0.05), but there was no added effect of ATL-146e. COX-1 expression was induced in macrophages (Mphis), whereas COX-2 was induced in neutrophils. Neither Hextend nor ATL-146e reduced COX expression. CONCLUSION: Hextend reduced the volume for initial resuscitation, which may offer logistical advantages in prehospital field conditions or whenever there is limited medical resources or prolonged transport times; ATL-146e improved early cardiac performance without causing hypotension or bradycardia; when administered 25 to 30 minutes after injury, neither Hextend nor ATL-146e altered inflammatory changes in pulmonary Mphis or infiltrating PMNs; and further studies are needed to determine whether these short-term benefits correlate with long-term outcome.

Animals↗
PubMed2003

Resuscitation with a novel hemoglobin-based oxygen carrier in a Swine model of uncontrolled perioperative hemorrhage.

BACKGROUND: Systemic and pulmonary hypertension, possibly related to nitric oxide scavenging by free hemoglobin (Hb), is often seen during resuscitation with hemoglobin-based oxygen carriers (HBOCs). Recently, a second-generation HBOC, rHb2.0 for Injection (rHb), has been developed using recombinant human Hb that has reduced reactivity with nitric oxide. The current study evaluates the efficacy of this novel compound for resuscitation in a swine model of uncontrolled perioperative hemorrhage. METHODS: After instrumentation, animals underwent splenectomy and rapid hemorrhage to a systolic blood pressure of 35 mm Hg and isoelectric electroencephalography. 15 minutes of shock was followed by resuscitation over 30 minutes. In phase I, 18 animals were randomized into three resuscitation groups: (1) lactated Ringer's (LR) equal to three times the shed blood, the negative control group; (2) heterologous blood (BL) equal to Hb 2 g/kg, the positive control group; and (3) rHb equal to 2 g/kg, the treatment group. In phase II, six animals underwent the same experiment with a first-generation HBOC, diaspirin cross-linked Hb (DCLHb) equal to 2 g/kg, an additional control group. On day 0 after 2 hours of observation, spontaneously breathing animals were returned to their cages. Surviving animals were redosed on days 1, 2, and 3 (rHb/DCLHb 1 g/kg; LR/BL-LR 500 mL). Survivors were killed on day 5 and organs harvested for histologic examination. Group comparisons were performed using Student's t test, repeated-measures analysis of variance, and chi2 test. Significance was set at 95% confidence intervals. RESULTS: After resuscitation, systemic mean arterial pressure (MAP) (baseline = 107 +/- 15 mm Hg) was 128 +/- 34 and 108 +/- 15 mm Hg in rHb and BL animals, respectively, and remained stable. In LR and DCLHb animals, after normalization, MAP declined to 67 +/- 13 and 84 +/- 34 mm Hg, respectively. The rHb group maintained higher MAP than the LR and BL groups (p < 0.05 vs. both). With resuscitation, mean pulmonary arterial pressure (PAP) (baseline = 25 +/- 5 mm Hg) increased in rHb (40 +/- 4 mm Hg), BL (34 +/- 3 mm Hg), and DCLHb (40 +/- 3 mm Hg) groups, but stayed elevated only in the DCLHb group (36 +/- 3 mm Hg). PAP in the rHb group was similar to the BL group (p > 0.05), and both rHb and BL groups showed a higher PAP than the LR group (p < 0.05 vs. both). PAP was highest in the DCLHb group (p < 0.05 vs. rHb). Cardiac output of rHb and BL groups was similar (p > 0.05) throughout the observation period. Arterial lactate increased to 5.6 +/- 2.5 mmol/L with shock and then normalized to < 2.0 mmol/L in the rHb, BL, and LR groups within 30 minutes of resuscitation. It remained elevated to > 3.5 mmol/L and showed a delayed increase in the DCLHb group (p < 0.05). Causes and number of deaths were as follows: rHb, zero of six; BL-transfusion reaction, one of six; LR-irreversible shock, four of six; and DCLHb-ventricular failure, six of six. There was no significant increase in plasma methemoglobin (rHb) and no difference in liver or cardiac enzymes (rHb vs. BL). No histologic abnormalities were seen in the rHb group except for cytoplasmic vacuolation, a process thought to be related to metabolism of the test article. CONCLUSION: rHb2.0 for Injection, a second-generation recombinant human HBOC, performs as well as heterologous blood for resuscitation after perioperative blood loss, does not cause sustained pulmonary hypertension, maintains adequate cardiac output and oxygen delivery, and is superior to either LR or DCLHb.

Animals↗
PubMed2002

Lung contusion: pathophysiology and management.

Management of severe pulmonary contusion is a challenge for clinicians. The incidence of adult respiratory distress syndrome (5-20%), pneumonia (5-50%), and mortality (5-10%) associated with traumatic lung injury has changed little in the past three decades. Therapeutic options are limited to basic supportive measures such as mechanical ventilation, positive end expiratory pressure, invasive cardiopulmonary monitoring, analgesics and aggressive pulmonary hygiene. Presently, no pharmacological agents can prevent the progressive respiratory embarrassment that is associated with the natural history of the disease, but several drugs have been tested in the laboratory. The purpose of this brief review is to summarize information published since January 2000 related to the clinical management and pathophysiology of lung contusion.

Journal Article↗
PubMed2002

Hemodynamic actions of acute ethanol after resuscitation from traumatic brain injury.

BACKGROUND: The purposes of this study were to determine how clinically relevant levels of acute ethanol (EtOH) influence cerebral perfusion pressure (CPP), cerebral venous O saturation (Scvo ), and systemic hemodynamics after fluid resuscitation from traumatic brain injury (TBI); and to test the hypothesis that the actions of EtOH on these variables are mediated by adenosine. METHODS: Anesthetized swine were ventilated (Fio = 0.4) and instrumented. In protocol 1, EtOH (3.5 g/kg, n = 11) or its vehicle (n = 17) was administered orally before TBI + 40% hemorrhage. At 90 minutes post-TBI, resuscitation consisted of shed blood + saline. In protocol 2, either saline (n = 15) or an adenosine-regulating agent (5-amino-4-imidazolecarboxamide riboside) in saline (1 mg/kg bolus + 12 mg/kg/h intravenously [i.v.]) (n = 5), was administered i.v. before TBI + 45% hemorrhage. At 90 minutes post-TBI, resuscitation consisted of saline only (three times shed blood volume). In protocol 3, EtOH was administered i.v. (1 g/kg; 20% vol/vol in saline) followed by either an adenosine receptor antagonist (theophylline, 10 mg/kg) or an adenosine uptake inhibitor (dipyridamole, 0.25 mg/kg). RESULTS: In protocol 1, with no EtOH, 11 of 17 (65%) survived post-TBI hypotension. Mean arterial blood pressure, cardiac index, and mixed venous oxygen saturation were stable for 1 hour at 40% to 60% below their respective baselines, whereas lactate increased three- to fourfold (all p < 0.05). After fluid resuscitation, most variables rapidly corrected, but intracranial pressure was increased 10 to 15 mm Hg (p < 0.05). With EtOH, 9 of 11 (82%) survived post-TBI hypotension (p = 0.42 vs. no EtOH). After resuscitation from TBI, there were significant effects of EtOH on systemic hemodynamics (mean arterial pressure, cardiac index, mixed venous oxygen saturation), on CPP, on lactate, and on Scvo at normo- and hypercapnia (all p < 0.05). The data from protocol 2 showed that essentially none of these changes were duplicated with an adenosine-regulating agent. In protocol 3, i.v EtOH produced small but significant changes in Scvo, intracranial pressure, and lactate, at normo-, hyper-, and hypocapnia. Dipyridamole and theophylline tended to have opposite, albeit small and not statistically significant, effects on these variables relative to EtOH alone.(2) (2) CONCLUSION: Acute EtOH (200-300 mg/dL) did not increase mortality after TBI + secondary hypotension, as long as cardiopulmonary support was provided. With EtOH, CPP was maintained and cerebral blood flow appeared to be adequate, if not excessive, with respect to cerebral metabolic demand, as judged by changes in Scvo at normo-, hyper-, and hypocapnia. These changes were probably not mediated, but might have been modulated, by increases in endogenous adenosine.

Alcoholic Intoxication↗
PubMed2002

Resuscitation from severe hemorrhagic shock after traumatic brain injury using saline, shed blood, or a blood substitute.

The original purpose of this study was to compare initial resuscitation of hemorrhagic hypotension after traumatic brain injury (TBI) with saline and shed blood. Based on those results, the protocol was modified and saline was compared to a blood substitute, diaspirin cross-linked hemoglobin (DCLHb). Two series of experiments were performed in anesthetized and mechanically ventilated (FiO2 = 0.4) pigs (35-45 kg). In Series 1, fluid percussion TBI (6-8 ATM) was followed by a 30% hemorrhage. At 120 min post-TBI, initial resuscitation consisted of either shed blood (n = 7) or a bolus of 3x shed blood volume as saline (n = 13). Saline supplements were then administered to all pigs to maintain a systolic arterial blood pressure (SAP) of >100 mmHg and a heart rate (HR) of <110 beats/min. In Series 2, TBI (4-5 ATM) was followed by a 35% hemorrhage. At 60 min post-TBI, initial resuscitation consisted of either 500 mL of DCLHb (n = 6) or 500 mL of saline (n = 5). This was followed by saline supplements to all pigs to maintain a SAP of >100 mmHg and a HR of <110 beats/min. In Series 1, most systemic markers of resuscitation (e.g., SAP, HR, cardiac output, filling pressures, lactate, etc.) were normalized, but there were 0/7 vs. 5/13 deaths within 5 h (P = 0.058) with blood vs. saline. At constant arterial O2 saturation (SaO2), mixed venous O2 saturation (SvO2), cerebral perfusion pressure (CPP), and cerebral venous O2 saturation (ScvO2) were all higher, intracranial pressure (ICP) was lower, and CO2 reactivity was preserved with blood vs. saline (all P < 0.05). In Series 2, SAP, ICP, CPP, and lactate were higher with DCLHb vs. saline (all P< 0.05). Cardiac output was lower even though filling pressure was markedly elevated with DCLHb vs. saline (both P< 0.05). Neither SvO2 nor cerebrovascular CO2 reactivity were improved, and ScvO2 was lower with DCLHb vs. saline (P < 0.05). All survived at least 72 h with neuropathologic changes that included sub-arachnoid hemorrhage, midline cerebellar necrosis, and diffuse axonal injury. These changes were similar with DCLHb vs. saline. Thus, whole blood was more effective than saline for resuscitation of TBI, whereas DCLHb was no more, and according to many variables, less effective than saline resuscitation. These experimental results are comparable to those in a recent multicenter trial using DCLHb for the treatment of severe traumatic shock. Further investigations in similar experimental models might provide some plausible explanations why DCLHb unexpectedly increased mortality in patients.

Animals↗