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Background The assessment of intravascular volume status is very important especially in children during anesthesia. Pulse pressure variation (PPV) and pleth variability index (PVI) are well known parameters for assessing intravascular volume status and fluid responsiveness. We compared PPV and PVI for children aged less than two years who underwent surgery in the prone position. Methods A total of 27 children were enrolled. We measured PPV and PVI at the same limb during surgery before and after changing the patients’ position from supine to prone. We then compared PPV and PVI at each period using Bland-Altman plot for bias between the two parameters and for any correlation. We also examined the difference between before and after the position change for each parameter, along with peak inspiratory pressure, heart rate and mean blood pressure. Results The bias between PPV and PVI was −2.2% with a 95% limits of agreement of −18.8% to 14.5%, not showing significant correlation at any period. Both PPV and PVI showed no significant difference before and after the position change. Conclusions No significant correlation between PVI and PPV was observed in children undergoing surgery in the prone position. Further studies relating PVI, PPV, and fluid responsiveness via adequate cardiac output estimation in children aged less than 2 years are required.

Hyperkalemia is sometimes life-threatening and is common in patients with severe renal insufficiency [1]. Some medications such as cyclooxygenase (COX-1, COX-2) inhibitors, angiotensin converting enzyme (ACE) inhibitors, and angiotensin II receptor blockers (ARBs) reduce the elimination of renal potassium resulting in hyperkalemia. Non-steroidal anti-inflammatory drugs (NSAIDs) are often prescribed as pain killers but have known adverse effects on kidney function. Thus, the elderly and patients at risk for diabetic nephropathy, long-lasting hypertension, or dehydration are more susceptible to the adverse effects of these drugs [2]. An episode of decreased renal function can be underestimated when the signs are asymptomatic, transitory, and non-anuric. Recently, ARBs have been prescribed in patients with hypertension to maintain appropriate renal perfusion by decreasing the glomerular filtration burden. ARBs protect renal and cardiac function by lowering oxidative stress, which is associated with chronic changes in the kidneys, heart, and blood vessels. However, ARBs decrease renal blood flow and reduce the elimination of potassium through the kidney under relatively dehydrated conditions [3] and a hypertensive state. Oral administration of ARBs in patients with chronic renal failure has resulted in serum potassium increases of up to 2 mEq/L during an operation. Although the patient was not suspected to have diabetic nephropathy because of normal creatinine clearance and negative urine protein, a preoperative ACE inhibitor and ARB prescription could lead to hyperkalemia and an abnormal electrocardiogram during an operation [4]. Dehydration has been discussed as a factor in reducing renal blood flow [5]. Thus, chronic administration of ARBs overlapped on possible preoperative dehydration can affect the elimination of potassium resulting in hyperkalemia. In addition to chronic treatment with an ARB, renal side effects of NSAIDs are relatively common and as prevalent as 5%. NSAIDs affect kidney function in two ways: interstitial nephritis due to an immunological reaction and prerenal failure due to reduced renal plasma flow [2]. Activating the renninangiotensin system to increase glomerular filtration pressure is necessary to maintain sufficient filtration. This physiological mechanism requires sufficient local synthesis of vasodilatory prostaglandins (PGE2, PGI2, PGD2) to counteract the action of angiotensin II on vascular tone. Because NSAIDs inhibit the PG-mediated vasodilation of afferent arterioles and glomerular capillaries, renal blood flow is critically affected in those patients at risk [2]. It is also advisable for anesthesiologists to consider the possibility of renal dysfunction in patients at risk with medication even though there is little chance to identify abnormal signs or abnormal laboratory nephropathy findings. It is more important to perform careful monitoring preoperatively and to evaluate renal function and effective circulatory volume.

Transfusion-free cardiac surgery in small cyanotic children is challenging to anesthesiologists because of cardiopulmonary bypass (CPB)-induced hemodilution and coagulopathy. Redo-complex cardiac procedures increase the incidence and volume of the transfusion [1]. Rastelli's procedure is a high risk procedure (RACHS; risk adjustment in congenital heart surgery category 4) and usually requires a blood transfusion. We present a 27 month-old girl (78.5 cm height and 7.7 kg weight) who was admitted for Rastelli's operation. The patient underwent the modified Blalock-Taussig shunt and patent ductus arteriosus closure 1 year ago without a transfusion. Her parents were Jehovah's Witnesses. They refused a perioperative blood transfusion, which included packed red blood cells, fresh frozen plasma, platelets, and albumin. They also refused usage of a cell saver. The anesthesiologist explained acute normovolemic hemodilution (ANH) and the parents agreed to ANH with the understanding that the collected autologous blood was not separated from the patient. One week before the surgery, recombinant human erythropoietin (2000 IU) was administered three times per week and iron sucrose was administered every day to stimulate the patient's blood cell production. After treatment, the hematocrit (Hct) increased from 47.2 to 49.1%. Platelet count and coagulation factors were within the normal range. After induction of anesthesia, 10 mg/kg tranexamic acid was infused for 30 minutes, then a continuous infusion was started at a rate of 5 mg/kg/hr. Cerebral oximetry (INVOS 5100, Somanetics, NY, USA) monitoring was started and the initial regional cerebral oxygen saturation (rSO2) values were 48/47% on the right/left sides. For ANH, 190 ml of whole blood was withdrawn from the patient's central line to the blood bag (single-320 ml blood bag, Greencross, Seoul, Korea), which contained 44.8 ml of citrate phosphate dextrose adenine. The same volume of hydroxyethyl starch (Voluven®, Fresenius Kabi, Bad Homburg, Germany) was infused while collecting the blood. The Hct decreased from 45 to 35% after ANH. The changes in rSO2 were < 10% from baseline, and blood lactate was within the normal range during ANH. A high-performance, low prime volume oxygenator (RX-05™, Terumo, Tokyo, Japan) was used and the arterial line filter was excluded to minimize the priming volume for CPB. During CPB, the Hct and pH ranged from 24 to 28%, and from 7.23 to 7.33 respectively. Intraoperative changes in blood lactate during surgery were within the normal range. After weaning from CPB, the collected autologous blood was transfused after protamine administration. Total operation time was 7 h and 20 minutes. The estimated blood loss and urine output was 130 and 720 ml. The patient received 190 ml of autologous blood and 215 ml of other fluids. The hematologic data are shown in Table 1. Table 1 Changes in Hematological Data Erythropoietin and iron sucrose were re-started. The lowest hemoglobin concentration in the ward was 7.6 g/dl, which increased to 9.4 g/dl on day 13 after surgery. The patient was discharged on postoperative day 19 with oral iron therapy and no complications. Three important issues must be considered for transfusion-free surgery. First, the volume of red blood cells should be increased before surgery. Second, the volume of blood loss should be minimized during surgery. Third, bleeding should be prevented after surgery. The patient received erythropoietin and simultaneous oral iron supplementation preoperatively. These have been shown to promote red blood cell production and reduce allogenic blood transfusion in children undergoing open heart surgery [2]. ANH is a blood conservation method to collect a patient's red blood cells before or just after induction of anesthesia. In a previous report, the non-transfusion rate of Rastelli's procedure was only 17%, but it increased to 75% following autologous blood donation [3]. The ANH-induced decrease in Hct may have impaired tissue oxygenation. Therefore, target Hct was determined to be 35%, and 190 ml of blood was collected as calculated. During ANH, safety was assessed using vital signs, lactate values, and rSO2, which is a useful indicator of trends in cerebral oxygenation [4]. Complex transfusion-free procedures can be accomplished safely in pediatric patients with a miniaturized CPB system for low priming volume [5]. In our case, we used a neonatal CPB system (Heart-Lung machine HL 30™, Maquet, Hirrlingen, Germany) to reduce hemodilution and maintain adequate oxygen supply. Additionally, tranexamic acid was continuously infused during the operation to reduced intra- and post-operative blood loss. In summary, we performed a transfusion-free Rastelli's procedure in a child weighing 7.7 kg. We conclude that multidisciplinary approaches, including perioperative erythropoietin, ANH, a low-prime CPB circuit, and tranexamic acid, enable high risk transfusion-free cardiac surgery in children.

Anesthetics have been suspected of impairing various aspects of the immune function either directly by affecting the function of immunocompetent cells or indirectly by modulating the stress response. Splenocytes play important roles in the cellular host defense against infection. In order to assess the immune modulatory effects of propofol, this study examined the cytotoxic and proliferative effects of propofol on splenocytes. Methods: Splenocytes, as responders, were isolated from BALB/c mice (n = 10). The cells were pretreated with different propofol concentrations (0μM, 30μM, 100μM, 300μM) for 24 hours. The cytotoxic effect was assayed by the NADH dehydrogenase activity and the proliferation was evaluated by the level of 5-bromo-2’-deoxyunridine (BrdU) incorporation during DNA synthesis in the presence or absence of propofol, in addition to lipopolysaccharide (LPS, 1 μg/ml) for mitogenic stimulation. A cell proliferation enzyme-linked immuno-sorbent assay (ELISA) system was used, and the stimulation index was calculated in the presence or absence of propofol. Results: The percentage of the NADH dehydrogenase activity was changed by the propofol pretreatment (P ＜ 0.001). LPS stimulation significantly decreased the NADH dehydrogenase activity at 100μM and 300μM compared with the propofol-added or pretreated cells (P ＜ 0.05). The stimulation index to LPS was lower at concentrations of 100μM and 300μM than at 30μM, and proliferative response of splenocytes were completely abrogated by adding toxic concentrations (100μM) of propofol (P ＜ 0.05). Conclusions: Neither cytotoxicity, as defined by the NADH dehydrogenase activity, nor a proliferative effect, as measured by the level of (BrdU) incorporation in the splenocytes, were affected by the clinical concentration of propofol.

Background: Various aspects of immunological homeostasis are affected by anesthesia and surgery, including the function of immunocompetent cells and the modulation of stress responses. To evaluate immunologic changes that occurred following propofol and enflurane anesthesia, we evaluated the proliferative responsiveness of peripheral blood mononuclear cells (PBMC) in patients undergoing laparoscopic gynecologic surgery. Methods: PBMC were isolated from patients prior to anesthesia and on the first postoperative day (n = 10). The proliferative response was then evaluated based on the level of 5-bromo-2-deoxyunridine (BrdU) incorporation that occurred during DNA synthesisafter the induction of mitogenic stimulation by treatment with 1 μg/ml lipopolysaccharides (LPS). To accomplish this, cell proliferation was assayed by enzyme-linked immuno-sorbent assay (ELISA), after which a stimulation index was calculated. Results: Although the calculated stimulation index decreased in response to both propofol and enflurane anesthesia, the stimulation index did not differ significantly between groups. However, following stimulation with LPS, the stimulation index was significantly higher in the enflurane group than in the propofol group (P ＜ 0.05). Conclusions: Propofol and enflurane anesthesia inhibit the PBMC proliferation. However, the decrease in proliferation that occurred in response to enflurane was attenuated by LPS. (Korean J Anesthesiol 2008; 55: 467∼72)

Chronic pain is often associated with changes in the immune responses, which highlights the need for the aggressive pain control to obtain a better prognosis. This study examined splenic NK cell cytotoxicity in an attempt to assess the possible changes in the immune function under chronic neuropathic pain after a partial transsection of the sciatic nerve. Methods: After confirming tactile allodynia in response to the von Frey filament, a modified lactate dehydrogenase (LDH) release assay was used to determine the cytotoxic activity of splenic NK cells on the YAC-1 cell line in C3H/HeN (H-2k) mice (n = 6). NK cells as effector cells were mixed with YAC-1 cells as target cells (1 × 104/100μl), resulting in an effector-target ratio of 1：25, 1：50, 1：100 in the culture medium. Results: At 1 and 2 weeks after the nerve injury, all the subjects showed significant mechanical sensitivity compared with those observed before surgery. The percentage of NK cell cytotoxicity of the neuropathic mice increased significantly 1 week after the nerve injury but decreased within 2 weeks compared with the normal mice. Conclusions: In terms of the altered NK cell cytotoxicity, neuropathic pain can cause changes in the normal performance of the immune function.

Background: Chronic neuropathic pain is often associated with altered immune function and the modulated immune cell response play a role in neuropathic pain by experimental nerve injury. In order to assess the possible changes in lymphocytes function following peripheral mononeuropathy, this study examined the lymphocyte subpopulation of the spleen using the monoclonal antibodies against the membrane surface markers in neuropathic BALB/c mice by a partial transection of sciatic nerve (PST). Methods: After confirming tactile allodynia by paw withdrawal threshold, the splenic lymphocytes were stained with fluorescein isothiocyanate (FITC)-conjugated anti-mouse CD45R/B220 (B cell) and CD4 (helper/inducer T cell) or with phycoerythrin (PE)-conjugated anti-mouse CD90.2 (total T cell) and CD8 (suppressor/cytotoxic T cell). The proportions of subsets were analyzed using a FACScan laser flow cytometry system on postoperative day 5 and day 18 respectively. Results: PST induced a mechanical allodynia as verified by the von Frey test at both 5 and 8 days postoperatively compared to pre-surgery (P ＜ 0.05). Lymphocyte subpopulation was affected by PST. The prop ortion of CD4+ subset was significantly larger in the PST group than in the sham operated group on day 5, while the proportion of CD8+ subset was larger on day 18. In the PST group, there were significantchanges in the proportion of CD4+ on day 5 and in the proportion of CD8+ on day 18 (P ＜ 0.05) compared to pre-surgery. There were no significant fluctuations in the proportion of total splenic T cell and B cell subsets of PST group compared to sham operated group. Conclusions: These results suggest that development of mononeuropathy is responsible for the proportional changes in splenic lymphocyte subsets in mice. (Korean J Anesthesiol 2007; 53: S 42∼7)

Background: It is evident that inhalational anesthetics, such as nitrous oxide, possess a certain degree of myelodepressive effect in humans. However, unlike nitrous oxide, propofol is frequently recommended for the anesthesia of oncologic patients or for harvesting bone marrow from donors. To evaluate the possible toxicity of propofol on hematopoietic stem cells, the in vitro sensitivity of colony growth to propofol was assessed using murine clonogenic hematopoietic progenitor cells. Methods: Femoral and tibial marrow cells were obtained from 4- to 6-week-old male BALB/c mice. Propofol was diluted in culture medium (30, 300 and 1 mM) and added into methylcellulose semi-solid culture media. After 14 days of culturing, the numbers of colony-forming unit granulocyte/monocyte (CFU-GM) colonies were counted. An advance liquid culture (RPMI 1640) of 5 hours duration was also applied prior to culturing in semisolid media to assess the short term exposure toxicity. Results: The colony counts were significantly decreased compared to the control at higher concentrations than 1 mM (P ＜ 0.05). The pre-exposure to propofol did not affect the number CFU-GM colony count at the concentrations of 30 and 300 or under conditions of co-culture. Conclusions: No myelodepressive effect was observed in mouse bone marrow cells with exposure of propofol at concentrations under 300.

Background: Under normal conditions, cerebral blood flow is regulated as cerebral perfusion pressure changes (autoregulation). Inflammatory conditions like bacterial meiningitis result in a loss of cerebral autoregulation several hours after exposure to bacterial endotoxin. Endotoxin appears to produce effects via the production of reactive oxygen species, such as the superoxide anion. Methods: Cerebral blood flow (CBF) was measured by hydrogen clearance in anesthetized rats 30 minutes after intravenous endotoxin 5 mg/kg or normal saline (control). Mean arterial pressure was reduced from 100 mmHg to 80 mmHg and 60 mmHg by hemorragic hypotension, and cerebral blood flow was measured at each pressure. Results: In the control group, CBF did not change when arterial pressure was reduced to 80 mmHg (113.9 ml vs 111.9 ml), but declined significantly at 60 mmHg (113.9 ml vs 88.4 ml). In the group treated with endotoxin, both a reduction of mean arterial pressure to 80 mmHg (129.8 ml vs 101.8 ml) and 60 mmHg (129.8 ml vs 78.4 ml) caused a significant reduction in CBF, indicating that autoregualtion had been abolished. Conclusions: The results of this study indicate that within minutes of endotoxin exposure, CBF markedly increased, and that the autoregualtion of CBF was inhibited.

Background: Trauma, surgical stress, and anesthesia are often associated with postoperative immune suppression and an increased susceptibility to infection. The role of propofol in a patient who may be at the risk of impaired immune function is contradictory. To access the possible role of propofol on human immune function, we investigated the cytotoxic activity of mononuclear cells from peripheral blood. Methods: Healthy human mononuclear cells (MNCs) were isolated and stimulated with lipopolysaccharide (LPS) for 5 hrs. Activated MNCs were cultured in the presence of varying concentrations of propofol for 20 hrs and lactate dehydrogenase (LDH) release was measured to evaluate NMC cytotoxicity against K-562 cell target cells (cell to target 40：1). Results: Propofol exposure at concentrations of 1, 5 and 10/ml did not significantly affect LDH release from K-562 cells, but the cytotoxic activity of MNCs was significantly suppressed at a concentration of 50/ml. (P ＜ 0.01) Conclusions: Since the concentrations of 1, 5 and 10/ml of propofol are in the clinically acceptable range for sedation and anesthesia, this result suggest that propofol does not significantly alter the cytotoxicity of NMCs in septic conditions.

Background: Sepsis, surgical stress, and anesthesia are often associated with postoperative immune suppression and an increased susceptibility to infection. Apoptosis is an important mechanism of cell death in sepsis and Endotoxemia, and the apoptosis-induced loss of lymphocytes may be responsible for immune depression. To access the possible role of propofol on human immune function in sepsis, we investigated the apoptosis of mononuclear cells (MNCs) and lymphocyte from peripheral blood. Methods: Healthy human mononuclear cells were isolated and stimulated with lipopolysaccharide (LPS) for 5 hrs. And, activated MNCs were cultured in the presence of varying concentrations of propofol (1/ml, 5g/ml, 10/ml and 50/ml) for 20 hrs. The apoptotic indices of LPS-treated MNCs, monocytes and lymphocytes were calculated by flow cytometry using an Annexin-V-FLUOS staining kit. Results: Propofol exposure at 1, 5 and 10/ml did not significantly affect apoptosis of the LPS-treated MNCs, monocytes or lymphocytes, but a concentration of 50/ml increased the apoptosis of MNCs and lymphocytes significantly (P

Background: The increasing number of outpatient surgery which requiring the rapid, smooth induction of anesthesia with rapid recovery may lead to the use propofol or sevoflurane. Our objective was to compare the hemodynamic responses and recovery profiles obtained by sevoflurane inhalation with propofol infusion using a laryngeal mask airway (LMA) in an ambulatory setting. Methods: Forty patients undergoing knee arthroscopic surgery were randomized into two groups. The laryngeal mask airway insertion was accomplished by using the voluntary maximal vital capacity breathing method (VCB) with sevoflurane 7% in nitrous oxide 50% (sevoflurane group) or by the infusion of propofol (target: 7g/ml) (propofol group). Under BIS monitoring (40-60), anesthesia was maintained by sevoflurane (2-3%) or propofol (mge of 3.7-4.2g/ml) with spontaneous respiration. Time to loss of consciousness (LOC) and LMA insertion from induction of anesthesia, hemodynamic responses, end tidal CO and recovery profiles were evaluated. Results: The mean time to LOC and to successful LMA insertion were similar in the groups. Hemodynamic responses in the sevoflurane group were not significantly different from those of the propofol group. However, in both groups, systolic and diastolic blood pressure were lower at the time of loss of consciousness and 5 min of after LMA insertion versus preinduction and LMA insertion values (P

Background: Epidural coadministration of opioids and local anesthetics has provided excellent analgesia during the postoperative period. The appropriate amount of epidural morphine for pain control with minimum side effects has been studied. Recently, we gave 6 mg of epidural morphine for 2 day pain control and discovered it was a safe and effective dose like the previous study result. This study was performed to compare postoperative analgesia and side effects according to different loading and infusion doses of morphine with the same total dose. Methods: Forty-three patients having epiduro-general anesthesia for a hysterectomy were randomly divided into 2 groups. The patients received 2 mg (Control group, n = 19) or 3 mg (Experimental group, n = 24) of epidural morphine by bolus and a continuous epidural infusion was started using a two day infusor containing 4 mg (Control group) or 3 mg (Experimental group) of morphine in 100 ml of 0.125 % bupivacaine. Visual analog scale (V AS) for pain, severity of nausea, itching and respiratory depression were assessed at 2, 4, 8, 16, 32 and 48 hours postoperatively. All data was evaluated with unpaired t-test for significances between the two groups. Results: Analgesia between the two groups showed good results. The V AS in the experimental group were higher than the control group in the early postoperative period. Nausea scores were no different between the two groups. The itching scores in the experimental group were lower than the control group at postoperative 16 and 32 hours. No respiratory depression was reported in either group. Conclusions: This study suggests that different loading and infusion doses of the same total epidural morphine between two groups provided good postoperative pain relief without any differences in side effects.

There is no treatment either to prevent the development of complex regional pain syndromes (CRPS), or to adequately and specifically control established pain. Symptom-based analysis of pain is important for disease progress assessments and treatment outcomes. An intravenous regional block (IVRB) with local anesthetics can contribute to the management of CRPS. We observed that by the IVRB using ropivacaine, ketamine and clonidine, the patient with CRPS type I who was resistant to sympathetic ganglion block and medical treatment with gabapentin, carbamazepine and antidepressant, was relieved of neuropathic pain.