Medical and ethical challenges during the first successful human kidney transplantation in 1954 at Peter Bent Brigham Hospital, Boston.

BACKGROUND: The first successful major organ transplantation, a kidney transplant, took place on December 23, 1954, at Peter Bent Brigham Hospital, Boston, Massachusetts. This was the beginning of major organ transplants commonly performed today, heralding one of the most significant achievements of medicine. A half-century later, heart, liver, limb, and even face transplants have become standard practice. In this report, we explore details of the preparations, the ethical dilemmas and the unknowns, and how these issues were addressed and overcome. METHODS: Published works, hospital records, personal notes, and conversations with the individuals who participated in this event allowed us a unique opportunity to collect, analyze, and interpret the events. RESULTS: Several factors converged at Peter Bent Brigham Hospital to enable success. The department chair in medicine was committed to studying renal hypertension who then recruited others to work in this area. The department chair in surgery was committed to research, including making research results clinically useful. The chair of the anesthesia division was a technically skilled clinician, able to manage a previously unknown procedure. Finally, a suitable candidate for kidney transplant happened to have an identical twin brother, eliminating the issue of possible rejection. These factors aligned at the right time and place to transplant the first human kidney. CONCLUSIONS: Medical and ethical challenges dominated the scene of the first successful major organ transplant, which began the remarkable advance in transplant medicine, an advance that occurred very rapidly between 1947 and 1951.

Hypoventilation after inhaled anesthesia results in reanesthetization.

BACKGROUND: During emergence from volatile anesthesia, hypoventilation may result from many causes. In this study, we examined the effect of hypoventilation after initial emergence from volatile anesthesia and the potential for reanesthetization. METHODS: The uptake and excretion of desflurane (Des), sevoflurane, and isoflurane were studied using the Gas Man® computer simulation program for a 70-kg simulated patient. The vaporizer setting was adjusted so that a VRG (vessel-rich tissue group, including brain) level of 0.75 minimum alveolar concentration (MAC), 1.0 MAC, and 1.5 MAC was rapidly achieved and maintained within tight limits for a 1-, 2-, 4-, and 6-hour period of anesthesia.At the end of the simulated period of anesthesia, the vaporizer was set to 0 and fresh gas flow was set to 8 L/min. Ventilation (VA) was continued at 4 L/min until the anesthetic level in the VRG reached MAC awake, equal to 0.33 MAC for each drug. Then, the VA was adjusted to 0.1 L/min to simulate near-apnea and 0.0 L/min to simulate true apnea. Severe reanesthetization was said to occur if the VRG level increased to or above 0.5 MAC. Mild reanesthetization was said to occur if VRG increased from its value of 0.33 MAC but did not reach 0.5 MAC. The minimum VA required to avoid severe reanesthetization was studied by trials of decreased VA beginning at the time the VRG reached 0.33 MAC. RESULTS: After emergence from 1 hour of anesthesia, all simulated patients were protected against mild and severe reanesthetization if anesthesia was at 0.75 or 1.0 MAC. After 4 or 6 hours of anesthesia, severe reanesthetization occurred with all drugs with near or true apnea if anesthesia was at 1.0 or 1.5 MAC. The minimum alveolar VA to protect against severe reanesthetization after 6 hours of anesthesia was no more than 0.5 L/min for all drugs at 0.75 MAC, no more than 0.5 L/min at 1.0 MAC, and no more than 1.2 L/min at 1.5 MAC. In all simulated cases, the source of anesthetic drug that allowed reanesthetization was muscle (MUS), which reached a value of 0.8 MAC within 4 hours with all drugs and reached a value of 0.75 MAC with desflurane after 2 hours. Fat levels of anesthetic remained less than 0.15 MAC for all drugs up to the 6 hours tested. CONCLUSIONS: Reanesthetization from hypoventilation after inhaled anesthesia is possible. After initial emergence, muscle is a source of anesthetic and predisposes to reanesthetization while fat is a sink for anesthetic and fosters continued emergence. Severe hypoventilation will cause some degree of reanesthetization from anesthetic released from muscle after 4 hours of 1 MAC inhaled anesthesia with desflurane, sevoflurane, or isoflurane.

Kinetics of uptake and washout of lidocaine in rat sciatic nerve in vitro.

BACKGROUND: The potency and efficacy of local anesthetics injected clinically for peripheral nerve block depends strongly on the rate of neural drug uptake. However, because diffusion into surrounding tissues and removal by the vascular system are major factors in the overall distribution of lidocaine in vivo, true kinetics of drug/neural tissue interactions must be studied in the absence of those confounding factors. METHODS: Uptake: Ensheathed or desheathed isolated rat sciatic nerves were exposed to [(14)C]-lidocaine for 0 to 180 minutes and then removed and the lidocaine content of nerve and sheath analyzed. Washout: Isolated nerves were soaked in [(14)C]-lidocaine for 60 minutes and then placed in lidocaine-free solution for 0 to 30 minutes, with samples removed at different times to assess the drug content. Experimental variables included the effects of the ensheathing epineurium, lidocaine concentration, pH, presence of CO(2)-bicarbonate, and incubation duration. RESULTS: The equilibrium uptake of lidocaine increased with incubation time, concentration, and the fraction of molecules in the nonionized form. The uptake rate was unaffected by drug concentration, but was about halved by the presence of the epineurial sheath, with the washout rate slowed less. Slight alkalinization, from pH 6.8 to pH 7.4, by bicarbonate-CO(2) buffer or a nonbicarbonate buffer, enhanced the neural uptake, and to the same degree. The washout of lidocaine was faster after shorter incubations at high concentrations than when equal amounts of lidocaine were taken up after long incubations at low lidocaine concentrations. CONCLUSION: Lidocaine enters a nerve by a process other than free diffusion, through an epineurial sheath that is a slight obstacle. Given the rapid entry in vitro compared with the much smaller and transient content measured in vivo, it seems highly unlikely that lidocaine equilibrates with the nerve during a peripheral blockade.

Chemical mediators of inflammation and resolution in post-operative abdominal aortic aneurysm patients.

Temporal-metabolomic studies of local mediators during inflammation and its resolution uncovered novel pathways and mediators, e.g., lipoxins, resolvins, and protectins that stimulate key resolution responses. Since these studies were carried out with isolated human cells and in animal models, it is important to determine in humans whether temporal profiles between pro-inflammatory mediators and pro-resolving mediators are demonstrable in vivo. To this end, we examined patients undergoing abdominal aortic aneurysm (AAA) surgery. Profiles of mediators including eicosanoids were assessed in addition to pro-resolving mediators. The results demonstrate temporal relationships for local-acting peptides (e.g., VEGF, IL-10, TGF(ß)) and lipid mediators (leukotrienes and resolvins). In addition, profiles obtained for AAA patients divided into two groups based on their temporal profile: one group consistent with a pro-inflammatory and another with a resolving profile. Together, these translational metabolomic profiles demonstrate for the first time the temporal relationships between local mediators in humans relevant in inflammation resolution.