Near-total esophagectomy: the influence of standardized multimodal management and intraoperative fluid restriction.

BACKGROUND AND OBJECTIVES: Esophagectomy can be associated with high morbidity and mortality. We present our experience managing these patients using a standardized multimodal approach that emphasizes intraoperative fluid restriction and early extubation. METHODS: This case series includes 56 consecutive patients over a 2-year period (1999-2000) that underwent near-total esophagectomy at a high-volume center. Surgical approach was determined by patient and tumor characteristics; intraoperative fluid replacement was conservative; and patient-controlled epidural anesthesia/analgesia was used to promote early extubation, enteral feeding, and ambulation. RESULTS: Overall morbidity was 18%; in-hospital and 30-day mortality was zero. Intraoperative urinary volume averaged 0.57 mL/kg/h. No patient developed postoperative renal dysfunction or pulmonary complications. All patients were extubated in the operating room. First ambulation averaged 1.6 days after surgery. Median intensive care unit and hospital stays were 1 and 10 days, respectively. Side effects from thoracic epidural analgesia were minimal. CONCLUSIONS: Significant reduction in esophagectomy-related morbidity is possible using a standardized multimodal approach in routine clinical practice. Intraoperative fluid restriction may facilitate early extubation and reduce pulmonary complications without compromising renal function. This preliminary observation warrants further study in a randomized clinical trial.

A model to evaluate the pharmacokinetic and pharmacodynamic variables of extended-release products using in vivo tissue microdialysis in humans: bupivacaine-loaded microcapsules.

UNLABELLED: Biodegradable microcapsules produce an ultra-long duration of local anesthesia. We hypothesized that this duration is caused by the sustained-release of bupivacaine from the microcapsules into the surrounding tissue. Previous studies investigated the pharmacokinetics (PKs) of bupivacaine after release from microcapsules and absorption into the systemic circulation. Microdialysis sampling can determine the PKs of any drug at its site of injection. This study was performed to characterize the PKs of bupivacaine and dexamethasone released from microcapsules at a subcutaneous injection site over a 96-h period in volunteers. Bupivacaine concentrations were compared with clinical variables of local anesthetic blockade. This study demonstrates that bupivacaine is released in a sustained manner from microcapsules, that bupivacaine concentrations increase for 24-34 h after microcapsule injection, and that analgesia parallels the tissue bupivacaine concentration obtained by microdialysis. Analgesia was equally rapid in onset with aqueous and microcapsule bupivacaine (P = 0.23). Analgesia was still present at 78% of microcapsule-injected sites after 96 h, significantly longer than for aqueous bupivacaine (P < 0.001). Mild pruritus was the most common side effect, occurring with 56% of the microcapsule injections. Dexamethasone-containing bupivacaine microcapsules are well tolerated and produce a prolonged duration of skin analgesia. Systemic absorption of bupivacaine produces higher peak plasma levels after aqueous injection than after microcapsule injection, despite the injection of a threefold larger load of bupivacaine in the latter. IMPLICATIONS: Microcapsules loaded with bupivacaine and dexamethasone and administered by subcutaneous injection produce prolonged cutaneous anesthesia and analgesia. Determination of local tissue pharmacokinetic variables of bupivacaine by microdialysis confirms that the prolonged duration of anesthesia is caused by the extended release characteristics of the microcapsules.