Randy W. Loftus

Intraoperative Ketamine Reduces Perioperative Opiate Consumption in Opiate-dependent Patients with Chronic Back Pain Undergoing Back Surgery

Background:Ketamine is an N-methyl-d-aspartate receptor antagonist that has been shown to be useful in the reduction of acute postoperative pain and analgesic consumption in a variety of surgical interventions with variable routes of administration. Little is known regarding its efficacy in opiate-dependent patients with a history of chronic pain. We hypothesized that ketamine would reduce postoperative opiate consumption in this patient population. Methods:This was a randomized, prospective, double-blinded, and placebo-controlled trial involving opiate-dependent patients undergoing major lumbar spine surgery. Fifty-two patients in the treatment group were administered 0.5 mg/kg intravenous ketamine on induction of anesthesia, and a continuous infusion at 10 &mgr;g kg−1min−1 was begun on induction and terminated at wound closure. Fifty patients in the placebo group received saline of equivalent volume. Patients were observed for 48 h postoperatively and followed up at 6 weeks. The primary outcome was 48-h morphine consumption. Results:Total morphine consumption (morphine equivalents) was significantly reduced in the treatment group 48 h after the procedure. It was also reduced at 24 h and at 6 weeks. The average reported pain intensity was significantly reduced in the postanesthesia care unit and at 6 weeks. The groups had no differences in known ketamine- or opiate-related side effects. Conclusions:Intraoperative ketamine reduces opiate consumption in the 48-h postoperative period in opiate-dependent patients with chronic pain. Ketamine may also reduce opioid consumption and pain intensity throughout the postoperative period in this patient population. This benefit is without an increase in side effects.

Glucocorticoid Induction of Epithelial Sodium Channel Expression in Lung and Renal Epithelia Occurs via trans-Activation of a Hormone Response Element in the 5′-Flanking Region of the Human Epithelial Sodium Channel α Subunit Gene

In airway and renal epithelia, the glucocorticoid-mediated stimulation of amiloride-sensitive Na+ transport is associated with increased expression of the epithelial Na+ channel α subunit (αENaC). In H441 lung cells, 100 nm dexamethasone increases amiloride-sensitive short-circuit current (3.3 μA/cm2 to 7.5 μA/cm2), correlating with a 5-fold increase in αENaC mRNA expression that could be blocked by actinomycin D. To explore transcriptional regulation of αENaC, the human αENaC 5′-flanking region was cloned and tested in H441 cells. By deletion analysis, a ∼150-base pair region 5′ to the upstream promoter was identified that, when stimulated with 100 nm dexamethasone, increased luciferase expression 15-fold. This region, which contains two imperfect GREs, also functioned when coupled to a heterologous promoter. When individually tested, only the downstream GRE functioned in cis and bound GR in a gel mobility shift assay. In the M-1 collecting duct line Na+ transport, mαENaC expression and luciferase expression from αENaC genomic fragments were also increased by 100 nm dexamethasone. In a colonic cell line, HT29, trans-activation via a heterologously expressed glucocorticoid receptor restored glucocorticoid-stimulated αENaC gene transcription. We conclude that glucocorticoids stimulate αENaC expression in kidney and lung via activation of a hormone response element in the 5′-flanking region of hαENaC and this response, in part, is the likely basis for the up-regulation of Na+transport in these sites.

Transmission of pathogenic bacterial organisms in the anesthesia work area.

Background:The current prevalence of hospital-acquired infections and evolving amplification of bacterial resistance are major public health concerns. A heightened awareness of intraoperative transmission of potentially pathogenic bacterial organisms may lead to implementation of effective preventative measures. Methods:Sixty-one operative suites were randomly selected for analysis. Sterile intravenous stopcock sets and two sites on the anesthesia machine were decontaminated and cultured aseptically at baseline and at case completion. The primary outcome was the presence of a positive culture on the previously sterile patient stopcock set. Secondary outcomes were the number of colonies per surface area sampled on the anesthesia machine, species identification, and antibiotic susceptibility of isolated organisms. Results:Bacterial contamination of the anesthesia work area increased significantly at the case conclusion, with a mean difference of 115 colonies per surface area sampled (95% confidence interval [CI], 62–169; P < 0.001). Transmission of bacterial organisms, including vancomycin-resistant enterococcus, to intravenous stopcock sets occurred in 32% (95% CI, 20.6–44.9%) of cases. Highly contaminated work areas increased the odds of stopcock contamination by 4.7 (95% CI, 1.42–15.42; P = 0.011). Contaminated intravenous tubing was associated with a trend toward increased nosocomial infection rates (odds ratio, 3.08; 95% CI, 0.56–17.5; P = 0.11) and with an increase in mortality (95% CI odds ratio, 1.11–∞; P = 0.0395). Conclusions:Potentially pathogenic, multidrug-resistant bacterial organisms are transmitted during the practice of general anesthesia to both the anesthesia work area and intravenous stopcock sets. Implementation of infection control measures in this area may help to reduce both the evolving problem of increasing bacterial resistance and the development of life-threatening infectious complications.

Hand contamination of anesthesia providers is an important risk factor for intraoperative bacterial transmission.

BACKGROUND:We have recently shown that intraoperative bacterial transmission to patient IV stopcock sets is associated with increased patient mortality. In this study, we hypothesized that bacterial contamination of anesthesia provider hands before patient contact is a risk factor for direct intraoperative bacterial transmission. METHODS:Dartmouth–Hitchcock Medical Center is a tertiary care and level 1 trauma center with 400 inpatient beds and 28 operating suites. The first and second operative cases in each of 92 operating rooms were randomly selected for analysis. Eighty-two paired samples were analyzed. Ten pairs of cases were excluded because of broken or missing sampling protocol and lost samples. We identified cases of intraoperative bacterial transmission to the patient IV stopcock set and the anesthesia environment (adjustable pressure-limiting valve and agent dial) in each operating room pair by using a previously validated protocol. We then used biotype analysis to compare these transmitted organisms to those organisms isolated from the hands of anesthesia providers obtained before the start of each case. Provider-origin transmission was defined as potential pathogens isolated in the patient stopcock set or environment that had an identical biotype to the same organism isolated from hands of providers. We also assessed the efficacy of the current intraoperative cleaning protocol by evaluating isolated potential pathogens identified at the start of case 2. Poor intraoperative cleaning was defined as 1 or more potential pathogens found in the anesthesia environment at the start of case 2 that were not there at the beginning of case 1. We collected clinical and epidemiological data on all the cases to identify risk factors for contamination. RESULTS:One hundred sixty-four cases (82 case pairs) were studied. We identified intraoperative bacterial transmission to the IV stopcock set in 11.5 % (19/164) of cases, 47% (9/19) of which were of provider origin. We identified intraoperative bacterial transmission to the anesthesia environment in 89% (146/164) of cases, 12% (17/146) of which were of provider origin. The number of rooms that an attending anesthesiologist supervised simultaneously, the age of the patient, and patient discharge from the operating room to an intensive care unit were independent predictors of bacterial transmission events not directly linked to providers. CONCLUSION:The contaminated hands of anesthesia providers serve as a significant source of patient environmental and stopcock set contamination in the operating room. Additional sources of intraoperative bacterial transmission, including postoperative environmental cleaning practices, should be further studied.

Reduction in intraoperative bacterial contamination of peripheral intravenous tubing through the use of a novel device.

Background:Hand hygiene is a vital intervention to reduce health-care associated infections, but compliance remains low. The authors hypothesized that improvements in intraoperative hand hygiene compliance would reduce transmission of bacteria to surgical patients and reduce the incidence of postsurgical healthcare-associated infections. Methods:The authors performed a controlled before-and-after study over 2 consecutive months. One hundred fourteen operative cases were enrolled. Two predesignated sites on the anesthesia machine were selected, decontaminated, and cultured via aseptic technique. These sites and the peripheral intravenous stopcock were cultured again after completion of the surgery. The treatment phase used a novel personal hand-decontamination device capable of recording hand-decontamination events. Results:There were no significant differences in patient location, age, or case duration and procedure type between groups. Use of the Sprixx GJ device (Harbor Medical Inc., Santa Barbara, CA) increased hourly hand decontamination events by 27-fold as compared with baseline rates (P < 0.002; 95% confidence interval, 3.3–13.4). Use of the device was associated with a reduction in contamination in the anesthesia work area and peripheral intravenous tubing. Intravenous tubing contamination was identified in 32.8% of cases in the control group versus 7.5% in the treatment group (odds ratio, 0.17; 95% confidence interval, 0.06–0.51; P < 0.01). Healthcare-associated infections rates were reduced in the device group (3.8%) as compared with the control group (17.2%) (odds ratio, 0.19; 95% confidence interval, 0.00–0.81; P = 0.02). Conclusions:Improved hand hygiene compliance through the use of a novel hand sanitation strategy reduces the risk of intraoperative bacterial transmission. The intervention was associated with a reduction in healthcare-associated infections.

Multiple reservoirs contribute to intraoperative bacterial transmission

BACKGROUND: Intraoperative stopcock contamination is a frequent event associated with increased patient mortality. In the current study we examined the relative contributions of anesthesia provider hands, the patient, and the patient environment to stopcock contamination. Our secondary aims were to identify risk factors for stopcock contamination and to examine the prior association of stopcock contamination with 30-day postoperative infection and mortality. Additional microbiological analyses were completed to determine the prevalence of bacterial pathogens within intraoperative bacterial reservoirs. Pulsed-field gel electrophoresis was used to assess the contribution of reservoir bacterial pathogens to 30-day postoperative infections. METHODS: In a multicenter study, stopcock transmission events were observed in 274 operating rooms, with the first and second cases of the day in each operating room studied in series to identify within- and between-case transmission events. Reservoir bacterial cultures were obtained and compared with stopcock set isolates to determine the origin of stopcock contamination. Between-case transmission was defined by the isolation of 1 or more bacterial isolates from the stopcock set of a subsequent case (case 2) that were identical to reservoir isolates from the preceding case (case 1). Within-case transmission was defined by the isolation of 1 or more bacterial isolates from a stopcock set that were identical to bacterial reservoirs from the same case. Bacterial pathogens within these reservoirs were identified, and their potential contribution to postoperative infections was evaluated. All patients were followed for 30 days postoperatively for the development of infection and all-cause mortality. RESULTS: Stopcock contamination was detected in 23% (126 out of 548) of cases with 14 between-case and 30 within-case transmission events confirmed. All 3 reservoirs contributed to between-case (64% environment, 14% patient, and 21% provider) and within-case (47% environment, 23% patient, and 30% provider) stopcock transmission. The environment was a more likely source of stopcock contamination than provider hands (relative risk [RR] 1.91, confidence interval [CI] 1.09 to 3.35, P = 0.029) or patients (RR 2.56, CI 1.34 to 4.89, P = 0.002). Hospital site (odds ratio [OR] 5.09, CI 2.02 to 12.86, P = 0.001) and case 2 (OR 6.82, CI 4.03 to 11.5, P < 0.001) were significant predictors of stopcock contamination. Stopcock contamination was associated with increased mortality (OR 58.5, CI 2.32 to 1477, P = 0.014). Intraoperative bacterial contamination of patients and provider hands was linked to 30-day postoperative infections. CONCLUSIONS: Bacterial contamination of patients, provider hands, and the environment contributes to stopcock transmission events, but the surrounding patient environment is the most likely source. Stopcock contamination is associated with increased patient mortality. Patient and provider bacterial reservoirs contribute to 30-day postoperative infections. Multimodal programs designed to target each of these reservoirs in parallel should be studied intensely as a comprehensive approach to reducing intraoperative bacterial transmission.

Ketamine/propofol admixture (ketofol) is associated with improved hemodynamics as an induction agent: a randomized, controlled trial.

BACKGROUND Critically ill patients may require emergent intubations, and the use of some induction agents can lead to undesirable effects on hemodynamics. The use of “ketofol” (ketamine/propofol admixture) may allow for improved hemodynamic control. The primary aim of this study was to assess the hemodynamic effects of “ketofol” in a fixed-dose combination during induction of general anesthesia in a controlled environment. METHODS This was a randomized, double-blinded, placebo-controlled trial conducted at the Dartmouth Hitchcock Medical Center. American Society of Anesthesiology physical status I and II patients undergoing general anesthesia were randomly assigned to standardized induction with propofol alone or with “ketofol.” Baseline noninvasive hemodynamic measurements were obtained and continuously monitored throughout the study period. Our hypothesis assumed that “ketofol” as an induction alternative would produce stable hemodynamics as referenced from baseline compared with propofol alone. The primary outcome was a systematic randomized assessment of changes in systolic blood pressure from baseline measurements for 30 minutes after induction. The primary comparisons were the frequency of a 20% change in systolic blood pressure at 5 minutes, 10 minutes, and 30 minutes after induction. RESULTS Baseline patient demographics and intraoperative characteristics were equivalent in both groups. Propofol was more likely to generate a 20% reduction in systolic blood pressure from baseline at 5 minutes (48.8% vs. 12%, odds ratio: 6.87, 95% confidence interval: 2.07–26.15, p = < 0.001) and 10 minutes (67.4% vs. 39%, odds ratio: 3.24, 95% confidence interval: 1.21–8.75, p = < 0.01) as compared with “ketofol.” This difference remained significant after adjustment for potentially confounding variables. CONCLUSION “Ketofol” is associated with improved hemodynamic stability during the first 10 minutes after induction. Further study is needed to assess the efficacy of “ketofol” in critically ill patients and those with significant comorbidities. This combination has the potential to be used as an alternative agent for emergency induction during which time stable hemodynamics are desirable. (J Trauma Acute Care Surg. 2012;73: 94–101. Copyright

Reduction in ventilator associated pneumonia in a mixed intensive care unit after initiation of a novel hand hygiene program.

PURPOSE Healthcare-associated infections (HCAIs) impact 10% of hospitalized patients. Some of these infections result from bacterial cross contamination and poor compliance with guidelines (Pittet D: Compliance with hand disinfection and its impact on hospital-acquired infections. J HospInfect 48 Suppl A:S40-S46, 2001); (Watanakunakorn C, Wang C, Hazy J: An observational study of hand washing and infection control practices by healthcare workers. Infect Control Hosp Epidemiol 19:858-860, 1998). Contamination of provider hands may be a modifiable risk factor. We instituted a novel multimodal system designed to improve hand hygiene by ICU providers. MATERIALS AND METHODS A before and after study design was used to evaluate the impact on the incidence of CRBSI and VAP of a multi-modal program incorporating education, performance feedback, and a body worn hand hygiene device. Compliance was communicated quarterly. Primary outcomes were CRBSIs and VAPs per 1,000 line days or per 1,000 ventilator days and compliance rates. Secondary outcomes were hospital length of stay and mortality. RESULTS A total of 1, 262 and 1,331 patients were evaluated during consecutive 12 month periods. VAP per 1000 vent days were significantly reduced after introduction of the program [3.7 vs. 6.9] P < .01. The reduction in CRBSI per 1000 line days was not significant [1.5 vs. 2.6], P = .09. Observed hand hygiene increased during the study period. There was no significant difference in mortality. CONCLUSIONS A novel multi-modal hand hygiene system resulted in a reduction in VAP. Provider hand contamination during patient care in the ICU is a modifiable risk factor for reducing ventilator associated pneumonias.

Video observation to map hand contact and bacterial transmission in operating rooms

BACKGROUND Hand hygiene (HH) is considered a primary intervention to avoid transmission of bacteria in health care settings and to prevent health care-associated infections. Despite efforts to decrease the incidence of health care-associated infections by improving HH, HH compliance rates vary widely depending on the hospital environment. METHODS We used intraoperative video observation to map temporal patterns of anesthesia provider hand contact with anesthesia work environment (AWE) surfaces and to assess HH compliance. Serial bacterial cultures of high contact objects were subsequently used to characterize bacterial transmission over time. RESULTS Using World Health Organization criteria, we found a large number of HH opportunities and a low rate of HH compliance by anesthesia providers (mean, 2.9%). We observed an inverse correlation between provider hand hygiene compliance during induction and emergence from anesthesia (3.2% and 4.1%, respectively) and the magnitude of AWE surface contamination (103 and 147 CFU, respectively) at these time points. We found no correlation between frequency of hand contact with the AWE and bacterial contamination. CONCLUSIONS Compliance with current HH recommendations by anesthesia providers is not feasible. However, there does appear to be a correlation between HH compliance rates and bacterial contamination of the AWE, an observation that should stimulate further work to design new methods for control of bacterial transmission in operating rooms.

Prevention of intravenous bacterial injection from health care provider hands: the importance of catheter design and handling.

BACKGROUND:Device-related bloodstream infections are associated with a significant increase in patient morbidity and mortality in multiple health care settings. Recently, intraoperative bacterial contamination of conventional open-lumen 3-way stopcock sets has been shown to be associated with increased patient mortality. Intraoperative use of disinfectable, needleless closed catheter devices (DNCCs) may reduce the risk of bacterial injection as compared to conventional open-lumen devices due to an intrinsic barrier to bacterial entry associated with valve design and/or the capacity for surface disinfection. However, the relative benefit of DNCC valve design (intrinsic barrier capacity) as compared to surface disinfection in attenuation of bacterial injection in the clinical environment is untested and entirely unknown. The primary aim of the current study was to investigate the relative efficacy of a novel disinfectable stopcock, the Ultraport zero, with and without disinfection in attenuating intraoperative injection of potential bacterial pathogens as compared to a conventional open-lumen stopcock intravascular device. The secondary aims were to identify risk factors for bacterial injection and to estimate the quantity of bacterial organisms injected during catheter handling. METHODS:Four hundred sixty-eight operating room environments were randomized by a computer generated list to 1 of 3 device-injection schemes: (1) injection of the Ultraport zero stopcock with hub disinfection before injection, (2) injection of the Ultraport zero stopcock without prior hub disinfection, and (3) injection of the conventional open-lumen stopcock closed with sterile caps according to usual practice. After induction of general anesthesia, the primary anesthesia provider caring for patients in each operating room environment was asked to perform a series of 5 injections of sterile saline through the assigned device into an ex vivo catheter system. The primary outcome was the incidence of bacterial contamination of the injected fluid column (effluent). Risk factors for effluent contamination were identified in univariate analysis, and a controlled laboratory experiment was used to generate an estimate of the bacterial load injected for contaminated effluent samples. RESULTS:The incidence of effluent bacterial contamination was 0% (0/152) for the Ultraport zero stopcock with hub disinfection before injection, 4% (7/162) for the Ultraport zero stopcock without hub disinfection before injection, and 3.2% (5/154) for the conventional open-lumen stopcock. The Ultraport zero stopcock with hub disinfection before injection was associated with a significant reduction in the risk of bacterial injection as compared to the conventional open-lumen stopcock (RR = 8.15 × 10−8, 95% CI, 3.39 × 10−8 to 1.96 × 10−7, P = <0.001), with an absolute risk reduction of 3.2% (95% CI, 0.5% to 7.4%). Provider glove use was a risk factor for effluent contamination (RR = 10.48, 95% CI, 3.16 to 34.80, P < 0.001). The estimated quantity of bacteria injected reached a clinically significant threshold of 50,000 colony-forming units per each injection series. CONCLUSIONS:The Ultraport zero stopcock with hub disinfection before injection was associated with a significant reduction in the risk of inadvertent bacterial injection as compared to the conventional open-lumen stopcock. Future studies should examine strategies designed to facilitate health care provider DNCC hub disinfection and proper device handling.