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Ketamine was reported to decrease cytokine production and improve survival after Escherichia coli-induced sepsis. We examined whether ketamine decreased interleukin (IL)-6 production and improved survival after 1) burn injury or 2) burn injury combined with sepsis (E. coli) at 24 h. Ketamine (10 mg/kg) or saline was given at 1 h after burn injury (G 1, 2, 5, 6), 24 h after burn injury (G 3, 4), or at E. coli inoculation (G 7, 8). Mortality was recorded for 7 days and IL-6 was measured in serum at 6 h after burn (G 1-2), 30 h after burn (G 3-4), or 6 h after sepsis (30 h after burn) (G 5-8). Burn injury only: Ketamine given immediately (1 h) after burn injury but not 24 h after, decreased the burn-induced increase of IL-6 but did not improve survival. Burn injury + sepsis: Ketamine given immediately after burn injury did not significantly decrease the sepsis-induced increase of IL-6 or improve survival. In contrast, ketamine given immediately after sepsis significantly improved survival (46.1% versus 13.3%, P = 0.008) and decreased IL-6 production (72,640 +/- 40,990 vs 332,300 +/- 32,300 pg/mL, P = 0.008). We conclude that ketamine therapy improves survival in burn injury followed by sepsis. This beneficial effect is probably achieved through interference with the inflammatory cascade, as evidenced by attenuation of the proinflammatory marker IL-6. more...

UNLABELLED Surgery is associated with activation of neutrophils and their influx into affected tissue. The pathogenic role of superoxide production generated by activated neutrophils has been documented repeatedly. Ketamine suppresses neutrophil oxygen radical production in vitro. In the present study, we compared the effect of adding small-dose ketamine to opioids during the induction of general anesthesia on superoxide production by neutrophils after coronary artery bypass grafting (CABG). Thirty-five patients undergoing elective CABG were randomized to one of two groups and prospectively studied in a double-blinded manner. The patients received either ketamine 0.25 mg/kg or a similar volume of saline in addition to large-dose fentanyl anesthesia. Blood samples were drawn before the operation, immediately after cardiopulmonary bypass, 24 and 48 postoperative h, and on postoperative Days 3-6. Functional capacity of neutrophils was assessed by superoxide generation after stimulation with phorbol 12-myristate 13-acetate, opsonized zymosan, or formyl-methionyl-leucyl-phenylalanine. The addition of small-dose ketamine to general anesthesia attenuates increased production of the superoxide anion (O2-) by neutrophils without chemical stimulation and after stimulation with phorbol 12-myristate 13-acetate, formyl-methionyl-leucyl-phenylalanine, and opsonized zymosan for 4-6 days after CABG. In addition, ketamine attenuated the percentage of neutrophils on postoperative Days 2-6. In the Control group, superoxide production significantly increased compared with the baseline value. By contrast, in the Ketamine group, this difference was not significant. IMPLICATIONS In a randomized, double-blinded, prospective clinical study, we compared the effect of adding small-dose ketamine to opioids during general anesthesia on superoxide production and showed that ketamine suppressed the increase of superoxide anion production by neutrophils after coronary artery bypass grafting. more...

Phenylephrine-induced hypertension (increase of 30-35 mm Hg for 15 min) is reported to increase cerebral perfusion pressure and collateral flow to ischemic areas of the brain in a rat model of focal cerebral ischemia. In the present study, we examined whether phenylephrine-induced hypertension of similar magnitude and duration was beneficial in a rat model of closed head trauma (CHT). Forty-eight rats were randomized into four experimental conditions: CHT at time 0 min (yes/no), plus phenylephrine-induced hypertension (increase of 30-35 mm Hg for 15 min) at 65 min (yes/no). CHT was delivered using a weight-drop device (0.5 J). Outcome measures were neurological severity score (NSS) at 1, 4, and 24 h, and brain tissue specific gravity (microgravimetry) and injury volume (2,3,5-triphenyltetrazoium chloride) at 24 h. After CHT, NSS at 24 h (median +/- range) and brain tissue specific gravity (mean +/- SD, injured hemisphere) were 7 +/- 2 and 1.033 +/- 0.007 without phenylephrine and 8 +/- 2 and 1.035 +/- 0.005 with phenylephrine (P = 0.43), respectively. Tissue injury volume (mean +/- SD) was 335 +/- 92 mm3 without phenylephrine and 357 +/- 154 mm3 with phenylephrine (P > 0.62). The results of our study indicate that postinjury treatment with 15 min of phenylephrine-induced hypertension does not attenuate brain edema, reduce tissue injury volume, or improve neurological outcome after CHT in rats. Implications: Phenylephrine-induced hypertension is reported to increase cerebral perfusion pressure and blood flow in a rat model of focal cerebral ischemia. In our study, phenylephrine-induced hypertension did not decrease brain edema or tissue injury volume or improve neurological outcome in a rat model of closed head trauma. (Anesth Analg 1998;87:574-8) more...

UNLABELLED Cardiopulmonary bypass (CPB) has been proposed as a model for studying the inflammatory cascade associated with the systemic inflammatory response syndrome. Serum interleukin-6 (IL-6) concentration seems to be a good indicator of activation of the inflammatory cascade and predictor of subsequent organ dysfunction and death. Prolonged increases of circulating IL-6 are associated with morbidity and mortality after cardiac operations. In the present study, we compared the effects of adding ketamine 0.25 mg/kg to general anesthesia on serum IL-6 levels during and after elective coronary artery bypass grafting (CABG). Thirty-one patients undergoing elective CABG were randomized to one of two groups and prospectively studied in a double-blind manner. The patients received either ketamine 0.25 mg/kg or a similar volume of isotonic sodium chloride solution in addition to large-dose fentanyl anesthesia. Blood samples for analysis of serum IL-6 levels were drawn before the operation; after CPB; 4, 24, and 48 h after surgery; and daily for 6 days beginning the third day postoperatively. Ketamine suppressed the serum IL-6 response immediately after CPB and 4, 24, and 48 h postoperatively (P < 0.05). During the first 7 days after surgery, the serum IL-6 levels in the ketamine group were significantly lower than those in the control group (P < 0.05). On Day 8 after surgery, IL-6 levels were no different from baseline values in both groups. A single dose of ketamine 0.25 mg/kg administered before CPB suppresses the increase of serum IL-6 during and after CABG. IMPLICATIONS In this randomized, double-blind, prospective study of patients during and after coronary artery bypass surgery, we examined whether small-dose ketamine added to general anesthesia before cardiopulmonary bypass suppresses the increase of the serum interleukin-6 (IL-6) concentration. Serum IL-6 levels correlate with the patient's clinical course during and after coronary artery bypass. Ketamine suppresses the increase of serum IL-6 during and after coronary artery bypass surgery. more...

In this study, we examined the effect of four i.v. fluids (250 mL/kg) on blood glucose and osmolality and brain tissue specific gravity after closed head trauma (CHT) in rats. CHT was delivered at Time 0; blood was sampled at 60 min; fluid infusion began at 75 min and ended at 105 min. Blood was again sampled at 105 and 120 min, and brain tissue specific gravity was determined at 120 min. Five groups (one control and four fluid-treated groups) received CHT, and five other groups (one control and four fluid-treated) did not (n = 9 in each group). 0.45% saline (1/2 NS) and 5% dextrose in water (D5W) accentuated the decrease of brain tissue specific gravity (1.0366 +/- 0.0025 and 1.0368 +/- 0.0028, respectively; mean +/- SD) caused by CHT (1.0395 +/- 0.0036), but 5% dextrose in 0.9% saline (D5NS) and 0.9% saline (NS) did not (1.0431 +/- 0.0042 and 1.0389 +/- 0.0049, respectively). In addition, 1/2 NS decreased blood osmolality (248 +/- 6 mOsm/L), D5W increased blood glucose (1095 +/- 173 mg/dL), D5NS increased blood osmolality (350 +/- 5 mOsm/L) and glucose (1695 +/- 76 mg/dL), and NS caused no significant change. We conclude that administering hypoosmolar i.v. fluids after CHT causes a significant worsening of cerebral edema 2 h after CHT. Implications We previously reported worse neurological outcome and/or mortality after closed head trauma in rats when 5% dextrose in water or 0.45% saline was given i.v. compared with 0.9% saline or 5% dextrose in 0.9% saline. The present results and our previous findings indicate that worsening of outcome after closed head trauma in rats may be caused more by edema formation than by hyperglycemia. more...

Hemorrhagic hypotension may aggravate the detrimental effects of head trauma on neurologic outcome. Our study examined whether using phenylephrine or large volumes of saline IV to increase mean arterial blood pressure (MAP) to 70, 80, or 90 mm Hg during the combination of head trauma and uncontrolled hemorrhage would improve neurologic outcome. Rats were assigned to one of 17 groups. In Groups 1-5, the variables were head trauma (yes/no), hemorrhage (yes/no), 0 or 3 mL saline per milliliter of blood lost, and no target MAP. In Groups 6-11, hemorrhage was or was not combined with head trauma, and large volumes of saline were given IV to achieve target MAPs of 70, 80, or 90 mm Hg. Groups 12-17 were similar to Groups 6-11 except that phenylephrine was used rather than saline to achieve target MAPs. Saline increased blood loss at 2 h to approximately 16 and 25 mL at a MAP of 80 and 90 mm Hg respectively, increased (worsened) the neurodeficit score but not cerebral edema at 24 h, and decreased survival rate at 2 and 24 h. Because phenylephrine was fatal for 62 of 63 rats, group mean values for blood loss, neurodeficit score, and brain tissue specific gravity could not be calculated. We conclude that supporting MAP with either phenylephrine or large volumes of saline worsened the neurodeficit score and/or survival and did not affect cerebral edema formation in our rat model of head trauma combined with hemorrhage.The results of this study indicate that maintaining mean arterial blood pressure at 70, 80, or 90 mm Hg with either phenylephrine or large volumes of saline worsened the neurodeficit score and/or survival and did not affect cerebral edema formation in our rat model of head trauma combined with hemorrhage. more...