ABSTRACT
Tracheal extubation requires careful planning and preparation. We present the extubation of a patient with severe ankylosing spondylitis after cervical spine surgery. We discuss the use of extracorporeal membrane oxygenation (ECMO) in this "at-risk" extubation, where our ability to oxygenate was uncertain and reintubation was predicted to be difficult. To our knowledge, ECMO has not previously been used in this context. We suggest preparing ECMO for rescue oxygenation when all other fundamental oxygenation techniques are predicted to be difficult or impossible. ECMO could be included in airway management and extubation guidelines.
Subject(s)
Airway Extubation , Extracorporeal Membrane Oxygenation , Aged , Cervical Vertebrae/injuries , Cervical Vertebrae/surgery , Fractures, Bone/surgery , Humans , Intubation, Intratracheal , Male , Spondylitis, Ankylosing/surgeryABSTRACT
Abstract In this study we explore if loss of GABAergic inhibitory interneurons in the superficial dorsal horn of the spinal cord contributes to reduced GABAergic tone and neuropathic pain following spinal cord injury (SCI). A moderate contusion injury to T11 resulted in the development of mechanical hyperalgesia and thermal hyperalgesia below the level of the lesion in gad1:GFP mice that were alleviated by IP administration of the GABA transporter antagonist tiagabine. Six weeks following SCI a decreased number of GFP(+) neurons were observed in the dorsal horn of SCI animals relative to sham mice. Tissue from a mouse 2 weeks post-SCI was subsequently observed to express activated caspase-3, indicative of apoptosis, co-localized to some GFP(+) GABAergic neurons. Glutamate decarboxylase (GAD)65 and GAD67 immunohistochemical staining was reduced in the dorsal horn of SCI animals. This observation was confirmed in Western blots showing reduced immunoreactivity for GAD67, as well as GABA transporter (GAT)1. Reversal of post-SCI neuropathic pain by tiagabine suggests that reduced GABAergic tone may contribute to hyperalgesia symptoms. This is supported by the subsequent observation that SCI reduced the number of GFP(+) inhibitory neurons, and the finding that some GABAergic GFP(+) neurons undergo cell death at a time point consistent with the development of neuropathic pain following SCI. Concordantly, reductions in both GAD65 and GAD67 and GAT1 immunoreactivity also support the observation of a loss of GABAergic inhibition and the associated spinal interneurons.
Subject(s)
Interneurons/metabolism , Nerve Degeneration/metabolism , Neuralgia/metabolism , Posterior Horn Cells/metabolism , Spinal Cord Injuries/metabolism , gamma-Aminobutyric Acid/deficiency , Animals , Apoptosis/genetics , Caspase 3/metabolism , Cell Count , Disease Models, Animal , Down-Regulation/genetics , GABA Agonists/pharmacology , GABA Plasma Membrane Transport Proteins/metabolism , GABA Uptake Inhibitors , Glutamate Decarboxylase/genetics , Glutamate Decarboxylase/metabolism , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Interneurons/pathology , Male , Mice , Mice, Transgenic , Nerve Degeneration/etiology , Nerve Degeneration/physiopathology , Neural Inhibition/drug effects , Neural Inhibition/genetics , Neuralgia/etiology , Neuralgia/physiopathology , Nipecotic Acids/pharmacology , Pain Measurement , Pain Threshold/physiology , Posterior Horn Cells/pathology , Promoter Regions, Genetic/genetics , Spinal Cord Injuries/complications , Spinal Cord Injuries/physiopathology , TiagabineABSTRACT
Local application of alphabetaMeATP (ligand for P2X3 receptors) and capsaicin (ligand for TRPV1 receptors) to the rat hindpaw produces pain behaviors (flinching) which are enhanced by noradrenaline (NA). In this study, we have examined the effect of nerve injury on adrenergic regulation of P2X3 and TRPV1 receptors by administering alphabetaMeATP and capsaicin, alone and in combination with NA, into the lateral and medial hindpaw in the spared nerve injury (SNI) model; this allows for an exploration of the role of injured and uninjured afferents in their effects on nociceptive signaling using a behavioral model. Following lateral hindpaw injections (sural sensory field), effects of NA and alphabetaMeATP, both alone and in combination, were increased following SNI, but no such effects were seen following medial hindpaw injections (saphenous sensory field). Following lateral hindpaw injections, the effect of capsaicin alone was unaltered following SNI, but the effect of NA/capsaicin was reduced; this latter effect was not seen following medial hindpaw injections. At the lateral site, prazosin (alpha1-adrenergic receptor antagonist) inhibited the effect of NA/alphabetaMeATP following SNI, but neither prazosin nor GF109203X (protein kinase C inhibitor) inhibited the effect of NA/capsaicin following SNI. These results demonstrate: (a) an enhanced adrenergic regulation of P2X3 receptor activity at lateral sites following SNI where signaling afferents are directly influenced by injured neurons; (b) differential effects on adrenergic regulation of TRPV1 receptors under the same conditions; (c) lack of such changes when agents are administered into medial sites following SNI.
Subject(s)
Peripheral Nerve Injuries , Receptors, Adrenergic, alpha-1/physiology , Receptors, Purinergic P2/physiology , TRPV Cation Channels/physiology , Adenosine Triphosphate/analogs & derivatives , Adenosine Triphosphate/pharmacology , Afferent Pathways/injuries , Afferent Pathways/physiology , Animals , Capsaicin/pharmacology , Hindlimb/innervation , Male , Norepinephrine/pharmacology , Pain/physiopathology , Rats , Rats, Sprague-Dawley , Receptors, Purinergic P2X3ABSTRACT
UNLABELLED: In the present study, the adrenergic receptor (AR) subtype mediating adrenergic augmentation of P2X(3) receptor-mediated nociceptive responses on sensory nerve endings was examined by using selective AR receptor agonists and antagonists in Sprague Dawley rats in the uninjured state. Local administration of alphabeta-methyleneATP (ligand for P2X3/P2X2/3 receptors) into the plantar hind paw produced few pain behaviors when given alone in this strain of rats; combination with adrenaline (alpha1- and alpha2-AR agonist) and phenylephrine (alpha1-AR agonist) but not clonidine or UK 14,304 (alpha2-AR agonists) increased flinching behaviors. Flinching produced by noradrenaline (NA)/alphabeta-methyleneATP was suppressed by low doses of prazosin (alpha1-AR antagonist), and this reduction was selective compared with yohimbine (alpha2-AR antagonist). Prazosin also reduced flinching produced by phenylephrine/alphabeta-methyleneATP. Using thermal threshold determinations, adrenaline and phenylephrine but not clonidine or UK 14,304, mimicked the action of NA in augmenting reductions in thermal thresholds produced by alphabeta-methyleneATP. Terazosin (another alpha1-AR antagonist) inhibited hyperalgesia produced by NA/alphabeta-methyleneATP. These results provide evidence for alpha1-AR involvement in adrenergic augmentation of P2X3/P2X2/3 receptor-mediated responses on sensory nerve endings in the uninjured state in Sprague Dawley rats. PERSPECTIVE: This study indicates the alpha1-adrenergic receptor subtype mediates adrenergic augmentation of the activation of sensory nerves by purinergic P2X3 receptors (respond to ATP) in the periphery. Observations are potentially relevant to chronic pain conditions in which sympathetic nerves influence sensory nerves.
