Lambert, Donald H. MD, PhD; Mustafa, Wissam MD; Rendon, Luis F. MD; Hartman, Ciana MPH; Xu, Lan PhD; Canelli, Robert MD Author Information

Background. Epidural analgesia is resource and labor intense and may limit postoperative management options and delay discharge. This study compared postoperative outcomes after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) with epidural analgesia versus continuous wound infusion system (CWIS) with/without intraoperative methadone. Methods. A single-institution, retrospective chart review was performed including all patients undergoing open CRS/HIPEC from 2018 to 2021. Patient demographics, surgical characteristics, length of stay, and in-hospital analgesic use were reviewed. In-hospital opioid exposure in morphine milligram equivalents (MME) was calculated. Multivariate analysis (MVA) for mean total and daily opioid exposure was conducted. Results. A total of 157 patients were included. Fifty-three (34%) had epidural analgesia, 96 (61%) had CWIS, and 79 (50%) received methadone. Length of stay was significantly shorter with CWIS + methadone versus epidural (7 vs. 8 days, p < 0.01). MVA showed significantly lower mean total and daily opioid exposure with CWIS+methadone versus epidural (total: 252.8 +/- 17.7 MME vs. 486.8 +/- 86.6 MME; odds ratio [OR] 0.72, 95% confidence interval [CI] 0.52-0.98, p = 0.04; Daily: 32.8 +/- 2.0 MME vs. 51.9 +/- 5.7 MME, OR 0.72, 95% CI 0.52-0.99, p <= 0.05). The CWIS-only group (n = 17) had a significantly lower median oral opioid exposure versus epidural (135 MME vs. 7.5 MME, p < 0.001) and longer length of stay versus CWIS + methadone (9 vs. 7 days, p = 0.04), There were no CWIS or methadone-associated complications and one epidural abscess. Conclusions. CWIS + methadone safely offers better pain control with less in-hospital opioid use, shorter length of stay, and decreased resource utilization compared with epidural analgesia in patients undergoing CRS-HIPEC.

A recent review suggests minimal respiratory depression (RD) after perioperative methadone, while another identified RD in up to 37 percent of patients. A meta-analysis is equivocal. At our institution, five of 75 opioid naive patients (6.6 percent) given perioperative methadone received naloxone. We report three of these cases in detail. Two others were discovered during an electronic medical record search for opioid naïve patients who received methadone plus naloxone during their anesthesia care. Our five patients indicate that RD owing to methadone can occur with excessive perioperative adjuvant medications and/or in patients who are taking home central nervous system depressants. We define perioperative adjuvant medications as medications given by the anesthesiologist prior to induction and intraoperatively. The risks and benefits of perioperative methadone administration, specifically in patients who received post-operative naloxone, deserve further investigation.

With aging-associated obesity and osteoarthritis, anesthesiology trainees and their instructors face difficulties in identifying the surface anatomy and landmarks for spinal anesthesia, and successfully advancing the needle into the intrathecal space. Through a series of illustrations and instructions, this teaching tool suggests that using a spinal needle in the same way that a blind person uses a white cane may improve a trainee’s ability to successfully perform a lumbar puncture. Reviewing the technique and instructions with the trainee before approaching the patient can minimize verbal instructions in the patient’s presence and may lead to improved efficiency and trainee success.

With the goal of improving patient safety, the Anesthesia Patient Safety Foundation published a statement that enhances existing monitoring.1 Recognizing the risk of awareness when using total intravenous anesthesia, especially when combined with neuromuscular agents, the Anesthesia Patient Safety Foundation now recommends using an encephalogram (EEG)-based monitor of unconsciousness during these procedures. This is the first time a recommendation has been made for using a depth of anesthesia monitor in the United States.

Anesthesiologist, Department of Anesthesiology, Boston Medical Center, Professor of Anesthesiology, Boston University School of Medicine, Boston, Massachusetts, [email protected]

A Hotline® fluid warmer is a device commonly used by anesthesia providers in the operating room to warm and infuse blood products and large fluid volumes. The purpose of the fluid warmer is to counter heat loss, which occurs under anesthesia. Despite normal checks performed prior to its use, we discovered a breach in the fluid warming set attached to the Hotline® fluid warmer during blood administration. The breach contaminated the patient’s sterile intravenous line. We describe the quality and safety processes we undertook in detail. We discuss the notion that monitoring alarms are an important safety feature of most modern devices utilized by anesthesia providers. We believe the Hotline® fluid warmer lacks a crucial monitor for detecting a breach within the fluid warming set, and therefore recommend the addition of an alarm to improve this device’s safety.

Recent data have demonstrated multiple benefits of intra- and postoperative fluid restriction in major abdominal surgery; however, data regarding the outcomes of fluid restriction in cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion (CRS/HIPEC) are limited. This study evaluates the safety and short-term clinical outcomes of restricted intraoperative fluid therapy in CRS/HIPEC.

To the Editor: The flexible cord wraps shown here are available online (search “gear ties”). They are quite useful for keeping monitor cables organized in the operating room and for patient transport. The bright green one pictured in Figure 1 is 18 inches long. I use 2 or 3 of them along the length of the cables.Figure 1.: The 18-inch tie wrapped around the monitoring cables near the operating room monitoring “brick.” The brick and organized cables are transferred to a transport monitor for patient transport.I use them to organize the cables before transporting the patient from the intensive care unit (ICU) to the operating room and back to the ICU (Fig. 2). The ICU staff appreciates it when patients return with the cables organized this way. I believe that organizing the cables this way minimizes the frustration associated with untangling “spaghetti.”Figure 2.: The cables organized with 3 cable wraps for patient transport.The bright colors keep the cable wraps from being lost. The cable wraps were approved for use by the medical center’s Value Analysis Committee. When our hospital’s infection control protocol is useda for the cleaning of all monitoring cables, the cable wraps are washed and disinfected easily between patients. Donald H. Lambert, PhD, MDDepartment of AnesthesiologyBoston University School of MedicineBoston, Massachusetts

Background Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are considered the standard of care for patients with peritoneal dissemination of appendiceal cancer and are increasingly being evaluated for use in patients with carcinomatosis from colon cancer. Mitomycin C (MMC) is one of the most frequently used HIPEC agents in the management of peritoneal-based gastrointestinal malignancies. This study analyzes the incidence and risk factors for developing neutropenia following MMC-HIPEC combined with CRS. Methods All patients undergoing CRS and MMC-HIPEC for appendiceal cancer between January 1993 and October 2006 were retrospectively reviewed. Logistic regression was used to identify risk factors for the development of neutropenia, defined as an absolute neutrophil count (ANC) <1,000/mm 3 . Results One hundred and twenty MMC-HIPEC were performed in 117 patients with appendiceal cancer. The incidence of neutropenia was 39%. Neutropenia occurred in 57.6% of female and 21.3% of male patients ( p < 0.0001). Female gender and MMC dose per body surface area (BSA) were independent risk factors for neutropenia on multivariable logistic regression [odds ratio (OR) of neutropenia in females = 3.58 (95% confidence interval, CI: 1.52, 8.43); OR for 5 unit (mg/m 2 ) increase in MMC dose per BSA = 3.37 (95% CI: 1.72, 6.63)]. Neutropenia did not increase the risk of mortality, postoperative infection or length of hospital stay. Conclusion Neutropenia is a frequent complication associated with MMC-HIPEC. Female sex and MMC dose per BSA are independent risk factors for neutropenia. These differences must be considered in the management of patients undergoing MMC-HIPEC to minimize the toxicity of the procedure.

Doxorubicin is a genotoxic chemotherapy agent used in treatment of a wide variety of cancers. Significant clinical side effects, including cardiac toxicity and myelosuppression, severely limit the therapeutic index of this commonly used agent and methods which improve doxorubicin efficacy could benefit many patients. Because doxorubicin cytotoxicity is cell cycle specific, the cell cycle is a rational target to enhance its efficacy. We examined the direct, cyclin-dependent kinase inhibitor roscovitine as a means of enhancing doxorubicin cytotoxicity. This study showed synergistic cytotoxicity between doxorubicin and roscovitine in three sarcoma cell lines: SW-982 (synovial sarcoma), U2OS-LC3-GFP (osteosarcoma), and SK-LMS-1 (uterine leiomyosarcoma), but not the fibroblast cell line WI38. The combined treatment of doxorubicin and roscovitine was associated with a prolonged G(2)-M cell cycle arrest in the three sarcoma cell lines. Using three different methods for detecting apoptosis, our results revealed that apoptotic cell death did not account for the synergistic cytotoxicity between doxorubicin and roscovitine. However, morphologic changes observed by light microscopy and increased cytoplasmic LC3-GFP puncta in U20S-LC3-GFP cells after the combined treatment suggested the induction of autophagy. Induction of autophagy was also shown in SW-982 and SK-LMS-1 cells treated with both doxorubicin and roscovitine by acridine orange staining. These results suggest a novel role of autophagy in the enhanced cytotoxicity by cell cycle inhibition after genotoxic injury in tumor cells. Further investigation of this enhanced cytotoxicity as a treatment strategy for sarcomas is warranted.

Boston University Medical School, Boston Medical Center, Boston, Massachusetts. donlam@fastmail.usor donald.lambert@bmc.orgThe editorial “Gloved and Masked—Will Gowns Be Next?” by Hepner1is both interesting and disconcerting. The main reason surgeons resist neuraxial anesthesia is because “It takes too long!” For this reason, it is frightening to see the rubric “Will gowns be next?” Demanding that anesthesiologists wear gowns to perform neuraxial anesthesia will, in my opinion, be the death knell for spinal and epidural anesthesia. Locating and donning a gown for these procedures will obviously not make doing them less time-consuming. More importantly, is it even necessary?Despite outcome data demonstrating a 1:10,000 to 1:50,000 risk of post–dural puncture meningitis, Dr. Hepner bases his recommendations for using gowns during neuraxial anesthesia on logic: “we must institute uniform sterile safety practices that have been proven, or seem by common logic to be prudent, and continue to study techniques used in other arenas [infection owing to central venous catheters (CVCs)] to determine their utility.”1That is, if gowns and full barriers are better for CVC insertions, it is logical that they are also good for neuraxial anesthesia.In the study showing that full-barrier precautions (sterile gloves, long-sleeved sterile gown, mask, cap, and large sterile sheet drape) reduced the incidence of CVC-related bloodstream infection compared with standard precautions (sterile gloves and small drape), the incidences of infection were 4 of 176 patients (2.3%, full-barrier precautions) and 12 of 167 patients (7.2%, standard precautions).2The extrapolated CVC infection rate is 227:10,000 for full barrier and 718:10,000 for standard barrier.If the neuraxial anesthesia infection rates were the same as for CVC insertions, no one would argue against the use of neuraxial full-barrier precautions. However, infections associated with neuraxial anesthesia (assuming 1:10,000 with standard precautions) are 718 times less than the infection rate for CVC placement. Why do we need to look to the CVC data, which clearly are irrelevant to neuraxial infections, and why do we need to depend on logic when we have valid neuraxial outcome data? If a 1:10,000 infection risk for lumbar puncture is unacceptable, what risk is acceptable? How much better can we do with full-barrier precautions and at what cost? How will we know whether full-barrier precautions are better? Based on the data, one could argue that full barriers for neuraxial anesthesia are an illogical solution to a nonproblem.I have done many spinals and epidurals during 25 yr of practice. Fortunately, none have caused an infection. However, my numbers are not close to approaching 10,000. It is encouraging to learn from Baer's data3that the odds that I will have an infection are exceedingly low. I wear gloves and a cap when doing neuraxial anesthesia. Although I have not routinely done so, I will wash my hands before putting on sterile gloves because that will apparently easily and conveniently further lessen any risk. On the other hand, I am resisting the donning of a gown until there is more than “logic” to justify it. Doing so will only jeopardize neuraxial anesthesia by making it take longer than it already does.Boston University Medical School, Boston Medical Center, Boston, Massachusetts. donlam@fastmail.usor donald.lambert@bmc.org

To the Editor: In a recent article, Kopp et al. (1) claim the following: “The survival rate among these patients was similar to the overall rate for our series and suggests that neither the patient population nor the neurological outcome of patients included in the ASA Closed Claims Project is representative of those who arrest during neuraxial block.” This makes little sense because: The Closed Claims Database (CCDB) (2,3) is 60 times larger than Kopp's. The outcome at the Mayo Clinic should be better than at the varied hospitals represented in the CCDB, where fewer resources are available compared with a tertiary care facility. The distribution of serious outcomes in the CCDB does not necessarily match those from a single institution's sample. Because the CCDB arose from malpractice claims, there can be no meaningful statistical comparisons with the Mayo Clinic's, where cases not involving a malpractice claim are equally likely to be included as those that do. If all cardiac arrests owing to neuraxial anesthesia occurred in a hospital like the Mayo Clinic, the outcomes might be more favorable than reported by the CCDB. However, the CCDB appears sound and is probably more representative of what happens in the general population. Donald H. Lambert, PhD, MD Boston Medical Center Boston, MA [email protected]