The esophageal cooling device: A new temperature control tool in the intensivist's arsenal.

BACKGROUND: Therapeutic hypothermia has been demonstrated to improve neurological outcome in comatose survivors of cardiac arrest. Current temperature control modalities however, have several limitations. Exploring innovative methods of temperature management has become a necessity. METHODS: We describe the first use of a novel esophageal cooling device as a sole modality for hypothermia induction, maintenance and rewarming in a series of four postcardiac arrest patients. The device was inserted in a manner similar to standard orogastric tubes and connected to an external heat exchange unit. RESULTS: A mean cooling rate of 0.42 °C/hr (SD ± 0.26) was observed. An average of 4 hr 24 min (SD ± 2 hr 6 min) was required to reach target temperature, and this was maintained 90.25% (SD ± 16.20%) of the hypothermia protocol duration. No adverse events related to device use were encountered. Questionnaires administered to ICU nursing staff regarding ease-of-use of the device and its performance were rated as favorable. CONCLUSIONS: When used as a sole modality, objective performance parameters of the esophageal-cooling device were found to be comparable to standard temperature control methods. More research is required to further quantify efficacy, safety, assess utility in other patient populations, and examine patient outcomes with device use in comparison to standard temperature control modalities.

Temperature control in critically ill patients with a novel esophageal cooling device: a case series.

BACKGROUND: Mild hypothermia and fever control have been shown to improve neurological outcomes post cardiac arrest. Common methods to induce hypothermia include body surface cooling and intravascular cooling; however, a new approach using an esophageal cooling catheter has recently become available. METHODS: We report the first three cases of temperature control using an esophageal cooling device (ECD). The ECD was placed in a similar fashion to orogastric tubes. Temperature reduction was achieved by connecting the ECD to a commercially available external heat exchange unit (Blanketrol Hyperthermia - Hypothermia System). RESULTS: The first patient, a 54 year-old woman (86 kg) was admitted after resuscitation from an out-of-hospital non-shockable cardiac arrest. Shortly after admission, she mounted a fever peaking at 38.3 °C despite administration of cold intravenous saline and application of cooling blankets. ECD utilization resulted in a temperature reduction to 35.7 °C over a period of 4 h. She subsequently recovered and was discharged home at day 23. The second patient, a 59 year-old man (73 kg), was admitted after successful resuscitation from a protracted out-of hospital cardiac arrest. His initial temperature was 35 °C, but slowly increased to 35.8 °C despite applying a cooling blanket and ice packs. The ECD was inserted and a temperature reduction to 34.8 °C was achieved within 3 h. The patient expired on day 3. The third patient, a 47 year-old man (95 kg) presented with a refractory fever secondary to necrotizing pneumonia in the postoperative period after coronary artery bypass grafting. His fever persisted despite empiric antibiotics, antipyretics, cooling blankets, and ice packs. ECD insertion resulted in a decrease in temperature from 39.5 to 36.5 °C in less than 5 h. He eventually made a favorable recovery and was discharged home after 59 days. In all 3 patients, device placement occurred in under 3 min and ease-of-use was reported as excellent by nursing staff and physicians. CONCLUSIONS: The esophageal cooling device was found to be an effective temperature control modality in this small case series of critically ill patients. Preliminary data presented in this report needs to be confirmed in large randomized controlled trials comparing its efficacy and safety to standard temperature control modalities.

Lysophosphatidic acid: a potential mediator of osteoblast-osteoclast signaling in bone.

Osteoclasts (bone resorbing cells) and osteoblasts (bone forming cells) play essential roles in skeletal development, mineral homeostasis and bone remodeling. The actions of these two cell types are tightly coordinated, and imbalances in bone formation and resorption can result in disease states, such as osteoporosis. Lysophosphatidic acid (LPA) is a potent bioactive phospholipid that influences a number of cellular processes, including proliferation, survival and migration. LPA is also involved in wound healing and pathological conditions, such as tumor metastasis and autoimmune disorders. During trauma, activated platelets are likely a source of LPA in bone. Physiologically, osteoblasts themselves can also produce LPA, which in turn promotes osteogenesis. The capacity for local production of LPA, coupled with the proximity of osteoblasts and osteoclasts, leads to the intriguing possibility that LPA acts as a paracrine mediator of osteoblast-osteoclast signaling. Here we summarize emerging evidence that LPA enhances the differentiation of osteoclast precursors, and regulates the morphology, resorptive activity and survival of mature osteoclasts. These actions arise through stimulation of multiple LPA receptors and intracellular signaling pathways. Moreover, LPA is a potent mitogen implicated in promoting the metastasis of breast and ovarian tumors to bone. Thus, LPA released from osteoblasts is potentially an important autocrine and paracrine mediator - physiologically regulating skeletal development and remodeling, while contributing pathologically to metastatic bone disease. This article is part of a Special Issue entitled Advances in Lysophospholipid Research.

Lysophosphatidic acid signals through multiple receptors in osteoclasts to elevate cytosolic calcium concentration, evoke retraction, and promote cell survival.

Lysophosphatidic acid (LPA) is a bioactive phospholipid whose functions are mediated by multiple G protein-coupled receptors. We have shown that osteoblasts produce LPA, raising the possibility that it mediates intercellular signaling among osteoblasts and osteoclasts. Here we investigated the expression, signaling and function of LPA receptors in osteoclasts. Focal application of LPA elicited transient increases in cytosolic calcium concentration ([Ca(2+)](i)), with 50% of osteoclasts responding at approximately 400 nm LPA. LPA-induced elevation of [Ca(2+)](i) was blocked by pertussis toxin or the LPA(1/3) receptor antagonist VPC-32183. LPA caused sustained retraction of osteoclast lamellipodia and disrupted peripheral actin belts. Retraction was insensitive to VPC-32183 or pertussis toxin, indicating involvement of a distinct signaling pathway. In this regard, inhibition of Rho-associated kinase stimulated respreading after LPA-induced retraction. Real-time reverse transcription-PCR revealed transcripts encoding LPA(1) and to a lesser extent LPA(2), LPA(4), and LPA(5) receptor subtypes. LPA induced nuclear translocation of NFATc1 and enhanced osteoclast survival, effects that were blocked by VPC-32183 or by a specific peptide inhibitor of NFAT activation. LPA slightly reduced the resorptive activity of osteoclasts in vitro. Thus, LPA binds to at least two receptor subtypes on osteoclasts: LPA(1), which couples through G(i/o) to elevate [Ca(2+)](i), activate NFATc1, and promote survival, and a second receptor that likely couples through G(12/13) and Rho to evoke and maintain retraction through reorganization of the actin cytoskeleton. These findings reveal a signaling axis in bone through which LPA, produced by osteoblasts, acts on multiple receptor subtypes to induce pleiotropic effects on osteoclast activity and function.