Lev Greemberg

Postoperative Pain: The Effect of Low-dose Ketamine in Addition to General Anesthesia

In a randomized, double-blind study, postoperative pain was assessed in 22 patients undergoing elective open cholecystectomy with two types of anesthesia: standardized general anesthesia (control group), and low-dose ketamine as an addition to the same method of general anesthesia, before surgical incision (ketamine group). After the operation we found that the time from the end of surgery to the first request for analgesic was longer in the ketamine group. Postoperatively, patients in both groups were treated with patient-controlled analgesia (PCA) in exactly the same way. The major difference in the study was the reduced dose requirement of morphine in the ketamine group compared with the control group after the operation. The mean dose of morphine given in patients of the control group during the first 24 h was 48.7 mg vs 29.5 mg in the ketamine group. Mean visual analog scale (VAS) and verbal rating scale (VRS) were higher in patients in the control group during the first 5 h after surgery (P < 0.02), but between 5 and 24 h after surgery VAS and VRS were not significantly different (P > 0.05). Our results indicate that postoperative pain can be decreased when ketamine in low doses is added to general anesthesia before surgical stimulation.

Ketamine Attenuates the Interleukin-6 Response After Cardiopulmonary Bypass

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 patients clinical course during and after coronary artery bypass. Ketamine suppresses the increase of serum IL-6 during and after coronary artery bypass surgery. (Anesth Analg 1998;87:266-71)

Ketamine attenuates neutrophil activation after cardiopulmonary bypass.

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.

Development of Abdominal Pain and IBS Following Gynecological Surgery: A Prospective, Controlled Study

BACKGROUND & AIMS Irritable bowel syndrome (IBS) develops after bacterial enteritis that causes injury to the bowel mucosa. Its unclear whether abdominal pain or IBS results from gynecological surgery that could injure abdominopelvic nerves. The aim of this prospective, controlled study was to assess the incidence of pain or IBS in women undergoing elective gynecological surgery compared to non-surgical controls and to identify factors associated with their development. METHODS One hundred thirty-two women without GI symptoms undergoing elective gynecological surgery for non-painful conditions were compared with 123 non-surgery controls without GI symptoms. Socio-demographic, psychosocial, and surgery-related variables were potential predictor variables of pain at 3 and/or 12 months. RESULTS Three surgical patients (2.7%), but no controls, developed IBS at 12 months. Significantly more surgical patients had abdominal pain at 3 or 12 months (15.3% vs 3.6%, P=.003). No socio-demographic or surgery-related variables predicted pain development, but it was predicted by psychosocial factors including anticipation of difficult recovery from surgery (P=.01), perception of severity/constancy of illness (P=.04), and reduced sense of coherence (P=.01). CONCLUSIONS Among women undergoing gynecological for non-pain indications the development of IBS was not significantly greater than controls. However, abdominal pain did develop in 17% of women in the surgical group, suggesting that surgery facilitated its development. Notably, only psychosocial variables predicted pain development, implying that pain development associated with central registration and amplification of the afferent signal (via cognitive and emotional input) must be considered along with the peripheral injury itself. These findings contribute to understanding the pathophysiology of functional GI pain.

The effect of epidural analgesia on labor progress and outcome in nulliparous women.

Objective. The present study was designed to investigate the influence of epidural analgesia on labor progress and outcome in nulliparous women. Methods. A population-based study comparing women with and without epidural analgesia was conducted. Deliveries occurred during 1988–2006 at the Soroka University Medical Center. A multivariable logistic regression model with backward elimination was constructed to control for confounders. Results. During the study period there were 39 498 deliveries; epidural analgesia was given in 9960 (25.2%) of these. Using a multivariable analysis with backward elimination, the following conditions were significantly associated with the use of epidural analgesia: advanced maternal age, oligohydramnios, premature rupture of membranes, induction of labor, and Jewish (vs. Bedouin) ethnicity. These patients were more likely to deliver by cesarean delivery (CD; OR = 1.4, 95% CI 1.3–1.5; p < 0.001) and vacuum extraction (OR = 1.5, 95% CI 1.4–1.7; p < 0.001). After controlling for possible confounders such as macrosomia, failed induction, hypertensive disorders, gestational diabetes, maternal age, labor dystocia, and ethnicity, epidural analgesia was not found to be an independent risk factor for CD but rather a protective factor (OR = 0.9, 95% CI 0.8–0.9; p = 0.038). When vacuum extraction was the outcome variable, epidural analgesia was documented as an independent risk factor (OR = 1.1, 95% CI 1.01–1.3; p = 0.04). Conclusions. Epidural analgesia in nulliparous parturients increases the risk for labor dystocia and accordingly is an independent risk factor for vacuum extraction. Nevertheless, it does not pose an independent risk for cesarean delivery.

Novel use of neonatal cuffed tracheal tube to occlude tracheo-oesophageal fistula

The use of a cuffed tracheal tube is described to occlude the leak through a tracheo‐oesophageal fistula (TOF) in a neonate and prevent gastric dilatation during positive‐pressure lung ventilation.

Constipation does not develop following elective hysterectomy: A prospective, controlled study

Abstract  Although there have been reports that women develop constipation following hysterectomy, previous studies were either retrospective or uncontrolled. The aim of this prospective, controlled study was to assess whether constipation develops after elective hysterectomy. Women undergoing elective gynaecological surgery were compared to matched non‐surgery controls at enrolment and 3 and 12 months after surgery. The subset of women who underwent elective hysterectomy was the study group for the present report. Fifty‐eight of the 132 elective surgery patients underwent hysterectomy and were compared to 123 controls. There was no difference between the groups at any follow‐up point in functional constipation (P = 1.0), frequency of stools (P = 0.92), stool consistency (P = 0.42), straining (P = 0.43), feeling of obstruction (P = 0.6) or need to manually evacuate stool (P = 1.0). Significantly, more hysterectomy patients without baseline pain did develop abdominal pain at 3 or 12 months than non‐surgery controls (16.7%vs 3.6%, P = 0.008). We conclude that there was no significant change in bowel habit or stool characteristics in women undergoing hysterectomy even though many developed abdominal pain. This prospective, controlled study challenges existing data regarding the effect of hysterectomy on constipation.

Effect of Ketamine on Inflammatory and Immune Responses After Short- Duration Surgery in Obese Patients

In non-obese patients ketamine decreases inflammatory responses and prevents overexpression of immune re- sponses. Its effect in obese patients is unknown. This prospective, blinded, randomized controlled trial was designed to determine the effect of ketamine on cytokines and immune cell responses after short-duration surgery in obese patients. Thirty-six patients received either ketamine 0.15 mg/kg IV prior to induction of general anesthesia, or an equal volume of normal saline. Cytokine concentrations and immune cell responses were determined pre-operatively and at 4, 24, and 48 h after operation. Interleukin (IL)-6 production was significantly greater in the control group (126.0 ± 18.8 ng/ml, mean ± SEM, n = 19) than in the ketamine group (57.9 ± 8.4 ng/ml) at 4 h. At other time periods IL-6 and tumor necrosis factor � increased and IL-2, lymphocyte proliferation, and natural killer cell cytotoxity decreased compared to pre-operative values in the control group but not in the ketamine group. We conclude that effects of ketamine on inflammatory and immune re- sponses after short-duration surgery in obese patients are similar to those previously reported in non-obese patients.

Cesarean section by local anesthesia in patients with familial dysautonomia

We describe a 29-year-old patient with familial dysautonomia who underwent cesarean section because of severe intrauterine fetal growth retardation. The surgery was done after induction of local anesthesia to avoid the critical and sometimes fatal complications of general anesthesia known in patients with familial dysautonomia. Surgery was uneventful and almost painless. The postoperative period was without complications. Induction of local anesthesia for cesarean section may constitute a suitable alternative in patients with familial dysautonomia.

Intra-partum epidural analgesia in grandmultiparous women

Objective. The present study aimed to characterise grandmultiparous women receiving intra-partum epidural analgesia and investigate associations between this method of pain relief and labour outcomes in grandmultiparas. Methods. A population-based study was conducted comparing obstetric and perinatal characteristics of grandmultiparous women with and without epidural analgesia. Deliveries occurred during the years 1988–2006. Multiple logistic regression models were constructed to find independent risk factors associated with epidural analgesia, cesarean section and 1st stage labour dystocia. Results. Out of 41,488 deliveries to grandmultiparous women included in the study, intra-partum epidural analgesia was utilised in 877 (2.1%). Multivariate analysis revealed that grandmultiparas who received epidural pain relief were significantly older and more likely to suffer from pre-mature rupture of the membranes, polyhydramnion, oligohydramnion, labour induction and a macrosomic fetus. After controlling for potential confounding, use of epidural analgesia remained an independent risk factor for 1st stage labour dystocia (odds ratio (OR) = 1.5; 95% confidence interval (CI) = 1.08–2.2) and cesarean delivery (OR = 2.9; 95% CI = 2.4–3.5) in grandmultiparas. Conclusion. Grandmultiparous women who received intra-partum epidural analgesia have entirely different obstetric characteristics as compared with those who did not receive this method of pain relief. Although epidural use was demonstrated to be an independent risk factor for 1st stage labour dystocia and cesarean section in this population, residual confounding cannot be excluded.