Futile Treatment-A Review.

The main goal of intensive care medicine is helping patients survive acute threats to their lives, while preserving and restoring life quality. Because of medical advancements, it is now possible to sustain life to an extent that would previously have been difficult to imagine. However, the goals of medicine are not to preserve organ function or physiological activity but to treat and improve the health of a person as a whole. When dealing with medical futilities, physicians and other members of the care team should be aware of some ethical principles. Knowing these principles could make decision-making easier, especially in cases where legal guidelines are insufficient or lacking. Understanding of these principles can relieve the pressure that healthcare professionals feel when they have to deal with medical futility. Efforts should be made to promote an ethics of care, which means caring for patients even after further invasive treatment has been deemed to be futile. Treatments that improve patients' comfort and minimize suffering of both patients and their families are equally as important as those aimed at saving patients' lives.

Medical futility treatment in intensive care units.

OBJECTIVE: To investigate cases of potential medical futility treatment in intensive care unit (ICU). MATERIALS AND METHODS: Retrospective review of 1567 charts of patients treated during the three-year period (2012 - 2014) in the ICU of the University Hospital Centre Split, Croatia, was conducted. More detailed analysis of the deceased patients' (n=429) charts was performed to identify cases of potential medical futility treatment. There were 99 patients for which ICU treatment was questionable due to their low Glasgow coma scale (GCS) score. For those patients types and duration of treatment were analyzed. RESULTS: Among patients who were treated during that period, 27% had died. Treatment of 99 patients (6.3% of the deceased) was considered a potential medical futility. Mean age of those 99 patients was 68±14 years and the mean stay in the ICU was 14±11 days. They spent 1302 patient days in the ICU, of which 52% days they had GCS 3 score. They were treated with catecholamines during 40% of the patient days. Minimal therapy was provided during 44% of the patient days. CONCLUSIONS: Analysis of the deceased patients' charts in the ICU indicated that a certain percentage of patients did not need prolonged ICU treatment. Instead, they were supposed to be treated in a palliative care unit. To avoid medical futility treatment in ICUs, palliative care unit needs to be established, as well as protocols for determining medical futility cases and ethical committee that will decide which patients will be transferred to palliative care.

Near-infrared spectroscopy provides continuous monitoring of compromised lower extremity perfusion during cardiac surgery.

Near-infrared spectroscopy (NIRS) is more frequently used to monitor regional oxygenation/perfusion of the cerebral and somatorenal vascular bed during congenital heart surgery. However, NIRS probes can be placed elsewhere to assess regional perfusion. We report the intraoperative use of NIRS probes on both calves of an infant to continuously monitor changes in the regional oxygenation/perfusion of a lower extremity whose perfusion was compromised after femoral arterial line placement. The NIRS trend of the compromised limb was compared with the contralateral limb throughout congenital heart surgery including the period on cardiopulmonary bypass (CPB). Our case report illustrates that NIRS technology can be used to monitor ongoing lower extremity vascular compromise during congenital heart surgery when it is not practical to directly access and continuously assess the limb. Transient vascular compromise after invasive femoral arterial line or sheath placement for cardiac catheterization in small infants is not infrequent. NIRS technology in such circumstances may help to decide whether watchful waiting is acceptable or immediate interventions are indicated. Continuous NIRS monitoring showed that limb regional oxygenation remained depressed during CPB but dramatically increased in the post-CPB period.

Activation of 5-HT1A receptors in the preBötzinger region has little impact on the respiratory pattern.

The preBötzinger (preBötC) complex has been suggested as the primary site where systemically administered selective serotonin agonists have been shown to reduce or prevent opioid-induced depression of breathing. However, this hypothesis has not been tested pharmacologically in vivo. This study sought to determine whether 5-HT1A receptors within the preBötC and ventral respiratory column (VRC) mediate the tachypneic response induced by intravenous (IV) (±)-8-Hydroxy-2-diproplyaminotetralin hydrobromide (8-OH-DPAT) in a decerebrated dog model. IV 8-OH-DPAT (19 ± 2 µg/kg) reduced both inspiratory (I) and expiratory (E) durations by ∼ 40%, but had no effect on peak phrenic activity (PPA). Picoejection of 1, 10, and 100 µM 8-OH-DPAT on I and E preBötC neurons produced dose-dependent decreases up to ∼ 40% in peak discharge. Surprisingly, microinjections of 8-OH-DPAT and 5-HT within the VRC from the obex to 9 mm rostral had no effect on timing and PPA. These results suggest that the tachypneic effects of IV 8-OH-DPAT are due to receptors located outside of the areas we studied.

Opioid-induced Respiratory Depression Is Only Partially Mediated by the preBötzinger Complex in Young and Adult Rabbits In Vivo.

BACKGROUND: The preBötzinger Complex (preBC) plays an important role in respiratory rhythm generation. This study was designed to determine whether the preBC mediated opioid-induced respiratory rate depression at clinically relevant opioid concentrations in vivo and whether this role was age dependent. METHODS: Studies were performed in 22 young and 32 adult New Zealand White rabbits. Animals were anesthetized, mechanically ventilated, and decerebrated. The preBC was identified by the tachypneic response to injection of D,L-homocysteic acid. (1) The µ-opioid receptor agonist [D-Ala2,N-Me-Phe4,Gly-ol]-enkephalin (DAMGO, 100 µM) was microinjected into the bilateral preBC and reversed with naloxone (1 mM) injection into the preBC. (2) Respiratory depression was achieved with intravenous remifentanil (0.08 to 0.5 µg kg(-1) min(-1)). Naloxone (1 mM) was microinjected into the preBC in an attempt to reverse the respiratory depression. RESULTS: (1) DAMGO injection depressed respiratory rate by 6 ± 8 breaths/min in young and adult rabbits (mean ± SD, P < 0.001). DAMGO shortened the inspiratory and lengthened the expiratory fraction of the respiratory cycle by 0.24 ± 0.2 in adult and young animals (P < 0.001). (2) During intravenous remifentanil infusion, local injection of naloxone into the preBC partially reversed the decrease in inspiratory fraction/increase in expiratory fraction in young and adult animals (0.14 ± 0.14, P < 0.001), but not the depression of respiratory rate (P = 0.19). PreBC injections did not affect respiratory drive. In adult rabbits, the contribution of non-preBC inputs to expiratory phase duration was larger than preBC inputs (3.5 [-5.2 to 1.1], median [25 to 75%], P = 0.04). CONCLUSIONS: Systemic opioid effects on respiratory phase timing can be partially reversed in the preBC without reversing the depression of respiratory rate.

Automatic classification of canine PRG neuronal discharge patterns using K-means clustering.

Respiratory-related neurons in the parabrachial-Kölliker-Fuse (PB-KF) region of the pons play a key role in the control of breathing. The neuronal activities of these pontine respiratory group (PRG) neurons exhibit a variety of inspiratory (I), expiratory (E), phase spanning and non-respiratory related (NRM) discharge patterns. Due to the variety of patterns, it can be difficult to classify them into distinct subgroups according to their discharge contours. This report presents a method that automatically classifies neurons according to their discharge patterns and derives an average subgroup contour of each class. It is based on the K-means clustering technique and it is implemented via SigmaPlot User-Defined transform scripts. The discharge patterns of 135 canine PRG neurons were classified into seven distinct subgroups. Additional methods for choosing the optimal number of clusters are described. Analysis of the results suggests that the K-means clustering method offers a robust objective means of both automatically categorizing neuron patterns and establishing the underlying archetypical contours of subtypes based on the discharge patterns of group of neurons.

Pontine µ-opioid receptors mediate bradypnea caused by intravenous remifentanil infusions at clinically relevant concentrations in dogs.

Life-threatening side effects such as profound bradypnea or apnea and variable upper airway obstruction limit the use of opioids for analgesia. It is yet unclear which sites containing µ-opioid receptors (µORs) within the intact in vivo mammalian respiratory control network are responsible. The purpose of this study was 1) to define the pontine region in which µOR agonists produce bradypnea and 2) to determine whether antagonism of those µORs reverses bradypnea produced by intravenous remifentanil (remi; 0.1-1.0 µg·kg(-1)·min(-1)). The effects of microinjections of agonist [D-Ala(2),N-Me-Phe(4),Gly-ol(5)]-enkephalin (DAMGO; 100 µM) and antagonist naloxone (NAL; 100 µM) into the dorsal rostral pons on the phrenic neurogram were studied in a decerebrate, vagotomized, ventilated, paralyzed canine preparation during hyperoxia. A 1-mm grid pattern of microinjections was used. The DAMGO-sensitive region extended from 5 to 7 mm lateral of midline and from 0 to 2 mm caudal of the inferior colliculus at a depth of 3-4 mm. During remi-induced bradypnea (~72% reduction in fictive breathing rate) NAL microinjections (~500 nl each) within the region defined by the DAMGO protocol were able to reverse bradypnea by 47% (SD 48.0%) per microinjection, with 13 of 84 microinjections producing complete reversal. Histological examination of fluorescent microsphere injections shows that the sensitive region corresponds to the parabrachial/Kölliker-Fuse complex.