Masataka Yokoyama

Intensive Versus Intermediate Glucose Control in Surgical Intensive Care Unit Patients

OBJECTIVE The optimal perioperative blood glucose range to improve surgical site infection (SSI) in surgical intensive care unit (ICU) patients remains unclear. We sought to determine whether the incidence of SSI is reduced by perioperative intensive insulin therapy (IT). RESEARCH DESIGN AND METHODS Patients were randomly assigned to receive perioperative intensive IT, with a target blood glucose range of 4.4–6.1 mmol/L, or intermediate IT, with a target blood glucose range of 7.7–10.0 mmol/L in the surgical ICU. We defined the primary end point as the incidence of SSI. RESULTS Study participants were randomly assigned to glucose control with one of two target ranges: for 225 patients in the intermediate IT group or for 222 patients in the intensive IT group, respectively. No patients in either group became hypoglycemic (<4.4 mmol/L) during their stay in the surgical ICU. In our series, the rate of SSI after hepato-biliary-pancreatic surgery was 6.7%. Patients in the intensive IT group, compared with the intermediate IT group, had fewer postoperative SSIs (9.8% vs. 4.1%, P = 0.028) and a lower incidence of postoperative pancreatic fistula after pancreatic resection (P = 0.040). The length of hospitalization required for patients in the intensive IT group was significantly shorter than that in the intermediate IT group (P = 0.017). CONCLUSIONS We found that intensive IT decreased the incidence of SSI among patients who underwent hepato-biliary-pancreatic surgery: a blood glucose target of 4.4 to 6.1 mmol/L resulted in lower rate of SSI than did a target of 7.7–10.0 mmol/L.

The evaluation of the ability of closed-loop glycemic control device to maintain the blood glucose concentration in intensive care unit patients.

Objectives:Reduction in the variability of blood glucose concentration might be an important aspect of blood glucose management. A closed-loop glycemic control device (STG-22; NIKKISO, Tokyo, Japan) has been developed to maintain blood glucose levels within the target range through automatic infusion of insulin and glucose. We hypothesized that the STG-22 system could provide optimal blood glucose management without causing hypoglycemic events in patients admitted to intensive care units. In this study, we investigated the feasibility of glycemic control with the STG-22 system. Furthermore, we evaluated the variability in blood glucose concentration associated with the use of the STG-22 system. Design:Retrospective analysis. Setting:A five-bed medical/surgical intensive care unit in a university hospital. Patients:Two hundred eight patients admitted to the intensive care unit between August 2006 and July 2009. Interventions:None. Measurements and Main Results:We calculated the mean and sd of blood glucose concentrations in each patient during intensive insulin therapy (target range, 90–110 mg/dL) administered using STG-22. In addition, to evaluate the blood glucose control achieved using STG-22, the durations for which the blood glucose level was maintained at 70–110 mg/dL, 110–150 mg/dL, 150–180 mg/dL, and >180 mg/dL were calculated. The average operation time of STG-22 was 33.9 ± 42.4 hrs. The blood glucose level was maintained at 70–110 mg/dL for 49.5% of the study period; the corresponding values for 110–150 mg/dL, 150–180 mg/dL, and >180 mg/dL were 31.4%, 7.0%, and 6.9%, respectively. No hypoglycemic events occurred. The sd of blood glucose levels was 19.9 ± 10.9 mg/dL. After a level of 150 mg/dL was achieved, the sd of blood glucose was 12.6 ± 3.1 mg/dL. Conclusions:STG-22 can help maintain optimal blood glucose levels without causing hypoglycemia in patients admitted to the intensive care unit. In addition, the use of this device might help decrease the variability in blood glucose concentration. Further randomized clinical trials are required to elucidate whether the low glucose variability maintained using STG-22 can contribute to improving the outcomes of patients admitted to the intensive care unit.

Impact of Preoperative Environmental Enrichment on Prevention of Development of Cognitive Impairment following Abdominal Surgery in a Rat Model.

Background:Sustained neuroinflammation may contribute to the pathogenesis of postoperative cognitive dysfunction (POCD). Here, the authors evaluated the preventive effect of preoperative environmental enrichment (PEE) on the development of neuroinflammation and concomitant POCD in a rat abdominal surgery model. Methods:Young and aged rats were assigned to one of four groups using a 2 × 2 experimental design: PEE versus sedentary condition for 14 days, by abdominal surgery versus anesthesia alone (n = 8 in each group). After a 7-day postsurgical recovery period, cognitive function was assessed using a novel object recognition test, followed by measurement of hippocampal levels of proinflammatory cytokines. Under identical conditions, microglia were isolated from the hippocampus for assessment of cytokine response to lipopolysaccharide. Results:In the sedentary group, aged, but not young, rats receiving surgery showed memory deficits (novel object preference during testing phase of 54.6 ± 7.8% vs. 76.9 ± 11.3% in nonsurgery group, P < 0.05) and increased hippocampal levels of cytokines compared with nonsurgical rats. PEE had no effects on novel object preference in nonsurgery animals (78.6 ± 10.7%), whereas it attenuated surgery-induced impairment of novel object preference (70.9 ± 15.0%, P < 0.05 vs. sedentary/surgery group) as well as increase of cytokine levels in hippocampus. Furthermore, upon ex vivo stimulation with lipopolysaccharide, cytokines release from hippocampal microglia isolated from aged rats before intervention was significantly higher in comparison with young rats. PEE resulted in reduction of these age-related microglial phenotypic changes. Conclusions:PEE could prevent the development of neuroinflammation and related POCD in aged rats by reversion of a proinflammatory phenotype of hippocampal microglia.

Postoperative pain impairs subsequent performance on a spatial memory task via effects on N-methyl-d-aspartate receptor in aged rats

AIMS Pain may be associated with postoperative cognitive dysfunction (POCD); however, this relationship remains under investigated. Therefore, we examined the impact of postoperative pain on cognitive functions in aged animals. MAIN METHODS Rats were allocated to the following groups: control (C), 1.2 % isoflurane for 2 hours alone (I), I with laparotomy (IL), IL with analgesia using local ropivacaine (IL+R), and IL with analgesia using systemic morphine (IL+M). Pain was assessed by rat grimace scale (RGS). Spatial memory was evaluated using a radial maze from postoperative days (POD) 3 to 14. NMDA receptor (NR) 2 subunits in hippocampus were measured by ELISA. Finally, effects of memantine, a low-affinity uncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, on postoperative cognitive performance were tested. KEY FINDINGS Postoperative RGS was increased in Group IL, but not in other groups. The number of memory errors in Group I were comparable to that in Group C, whereas errors in Group IL were increased. Importantly, in Group IL+R and IL+M, cognitive impairment was not found. The memory errors were positively correlated with the levels of NMDA receptor 2 subunits in hippocampus. Prophylactic treatment with memantine could prevent the development of memory deficits observed in Group IL without an analgesic effect. SIGNIFICANCE Postoperative pain contributes to the development of memory deficits after anesthesia and surgery via up-regulation of hippocampal NMDA receptors. Our findings suggest that postoperative pain management may be important for the prevention of POCD in elderly patients.

Successful management of rocuronium-induced anaphylactic reactions with sugammadex: a case report

Sugammadex, a new reversal agent for rocuronium, encapsulates the rocuronium molecule and results in rapid reversal of rocuronium-induced neuromuscular blockade. A case in which sugammadex was used to treat an anaphylactic reaction that occurred after rocuronium is presented. The binding/encapsulation of rocuronium by sugammadex may selectively eliminate the antigenic quaternary ammonium activity of circulating rocuronium, and prevent the propagation of rocuronium-induced anaphylaxis.

Effect of Vasoconstrictive Agents Added to Lidocaine on Intravenous Lidocaine-induced Convulsions in Rats

BACKGROUND Epinephrine is reported to decrease the threshold of intravenous lidocaine-induced convulsions. However, the mechanism underlying this effect is not clear. Therefore, we carried out a study to examine the role of vasopressor-induced hypertension. METHODS Fifty-six awake Wistar rats were assigned to seven groups of eight. All groups received a continuous intravenous infusion of lidocaine at a rate of 4 mg.kg-1.min-1 until generalized convulsions occurred. The control group (group C) received plain lidocaine. The acute hypertensive groups received lidocaine with epinephrine (group E), norepinephrine (group N), or phenylephrine (group P) to increase mean arterial blood pressure (MAP) to 150 +/- 5 mmHg. Sodium nitroprusside (SNP) was added to prevent an increase in mean arterial pressure in the remaining three groups (vasopressor-SNP groups). RESULTS The acute hypertensive groups required significantly smaller cumulative doses of lidocaine to produce convulsions compared with control (C = 41.5 +/- 2.9 > E = 24.1 +/- 2.7, N = 27.1 +/- 2.8, P = 26.7 +/- 2.5 mg.kg-1; values are mean +/- SD, P E = 7.4 +/- 0.5, N = 7.9 +/- 0.6, P = 8.1 +/- 0.8 micrograms.ml-1, P E = 32.6 +/- 4.2, N = 34.5 +/- 4.8, P = 37.1 +/- 4.5 micrograms.g-1, P < 0.01) were less in the acute hypertensive groups at the onset of convulsions. In the vasopressor-SNP groups, the plasma and brain lidocaine concentrations at the onset of convulsions returned to the control values, although epinephrine and norepinephrine, but not phenylephrine, still decreased cumulative convulsant doses of lidocaine significantly (P < 0.01) compared with control (E + SNP = 30.8 +/- 2.9 < N + SNP = 34.8 +/- 2.8, P < 0.01) < P + SNP = 40.2 +/- 3.0 mg.kg-1, P < 0.01). The brain/plasma concentration ratios were similar for the seven groups. CONCLUSIONS An equal degree of acute hypertension induced by these three different vasopressors may play a role in reducing the threshold (plasma and brain lidocaine concentrations) as well as the cumulative convulsant doses associated with lidocaine-induced convulsions.

Complete Heart Block during Anesthetic Management in a Patient with Mucopolysaccharidosis Type VII

IT is believed that complete heart block is unlikely to occur in patients without preexisting left bundle branch block. We describe the occurrence of complete heart block during attempted placement of a central venous catheter in a child with mucopolysaccharidosis (MPS) type VII (Sly syndrome) without preexisting left bundle branch block. Numerous reports of anesthesia in patients with MPS have described airway management and respiratory complications. However, cardiac problems during anesthesia in patients with MPS should he considered important because of the possibility of preexisting cardiomyopathy or coronary stenosis.

Oral Carbohydrate Loading with 18% Carbohydrate Beverage Alleviates Insulin Resistance

Preoperative 12.6% oral carbohydrate loading is an element of the Enhanced Recovery After Surgery (ERAS) protocol aimed at alleviating postoperative insulin resistance; however, in Japan, beverages with 18% carbohydrate content are generally used for preoperative carbohydrate loading. We investigated the effect of 18% carbohydrate loading on alleviating insulin resistance. Six healthy volunteers participated in this crossover-randomized study and were segregated into 2 groups: volunteers in the carbohydrate-loading group (group A) who fasted from after 9 pm and ingested 375 mL of a beverage containing 18% carbohydrate (ArginaidWaterTM; Nestle, Tokyo, Japan) between 9 pm and 12 pm, and 250 mL of the same liquid at 6:30 am. Volunteers in control group (group B) drank only water. At 8:30 am, a hyperinsulinemic normoglycemic clamp was initiated. Glucose infusion rate (GIR) and levels of ketone bodies and cytokines (IL-1β, IL-6, and TNF-α) before clamping were evaluated. p<0.05 was considered statistically significant. Levels of blood glucose, insulin, and cytokines at the start of the clamp were similar in both the groups. The GIR in group A was significantly higher than that in group B (11.5±2.4 vs 6.2±2.2 mg/kg/min, p=0.005), while blood ketone body levels were significantly lower in group A (22±4 vs 124±119 μmol/L, p=0.04). Preoperative 18% carbohydrate loading could prevent the decrease in insulin sensitivity and suppress catabolism in healthy volunteers. Thus, carbohydrate loading with a beverage with 18% carbohydrate content might contribute to improvements in perioperative management.

Repeated intra-articular injections of acidic saline produce long-lasting joint pain and widespread hyperalgesia

Synovial fluid in inflamed joint shows a drop in pH, which activates proton‐gated ion channels in nociceptors. No studies have ever tried to develop and characterize acid‐induced joint pain.

Comparison of plasma lidocaine concentrations after injection of a fixed small volume in the stellate ganglion, the lumbar epidural space, or a single intercostal nerve.

We measured the plasma lidocaine concentrations after stellate ganglion block (SGB) and compared them with those after intercostal nerve block (ICNB) and epidural block (EB) using identical doses of lidocaine.Thirty patients undergoing SGB (n = 10), ICNB (n = 10), or EB (n = 10) in our pain clinic participated in this study. Six milliliters of 1% lidocaine was used for all nerve blocks. SGB was performed at the C6 transverse process, ICNB was performed on a single intercostal nerve, and epidural lidocaine was injected through the lumbar epidural catheter. After drug administration, venous blood samples were taken from an indwelling catheter in the arm every minute for the first 10 min and 15, 20, 30, 45, and 60 min thereafter. Plasma lidocaine concentrations were measured by using an enzyme immunoassay method. The SGB group showed significantly higher peak plasma lidocaine concentrations than other groups (SGB 1.65 +/- 0.21 [micro sign]g/mL, ICNB 0.89 +/- 0.12 [micro sign]g/mL, EB 0.91 +/- 0.19 [micro sign]g/mL; P < 0.01). The SGB group reached peak levels significantly faster than the other groups (SGB 3.4 +/- 1.0 min, ICNB 7.9 +/- 1.5 min, EB 6.9 +/- 0.7 min; P < 0.01). We conclude that the plasma lidocaine concentrations after SGB were higher than those after ICNB and EB when using small, equal doses of lidocaine. The high and rapid peak plasma lidocaine concentrations after SGB are probably related to the high vascularity of the injection site. Implications: Higher plasma concentrations of local anesthetics are reportedly obtained after multiple intercostal nerves blocks compared with those after other types of nerve blocks. Our results, however, showed that the peak plasma concentrations after stellate ganglion block were higher and faster than those after a single intercostal nerve block. (Anesth Analg 1998;87:112-5)